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i-like-it-when-ju-sleeps · 3 years

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I am the Apocalypse (Part 3)

Pairing: Jay Halstead x Sarah (OC)

Summary: Takes place during Chicago Fire 3x18. Sarah is a doctor at Med and in a long term relationshp with Jay. She is at Med when the grenade goes off.

Part 1

Part 2

The next hour was spent trying to help as many people as they could but at this point, they had seen everybody who needed to be seen and people were just really playing the waiting game. Sarah looked at the woman who was in the room with Hermann and came in, deciding to check on them.

“What you got?” She asked the two and Hermann answered instead of the woman.

“We need to patch in your boyfriend” he stated grimly, and the young woman nodded, getting her phone out.

“He was working with Marburg.” Sarah told the blonde woman as she listened to Jay’s information. “He injected himself with it.”

“What's Marburg?” Hermann asked.

“It's a viral hemorrhagic fever. The Soviets developed it as a biological weapon. Ask them which strain of the Marburg virus.”

“Yeah, which strain?” Sarah transmitted over the phone and listened intently before answering the woman. “Raven.”

“Okay. All right. Okay, so now I just have to see if he was past the incubation period and actually infectious.” She stated clearly and the doctor and the firefighter looked at her expectantly.

“And if he was past the incubation period?” Hermann asked worriedly.

“It means Aleem was a walking biological weapon.” Diane announced and the three of them shared a look before glancing at all of the people outside.

“Alright,” Sarah sighed “Keep me posted, okay?” she asked the other woman before returning outside the room. The ER was still dark and filled with smoke, people anxiously waiting against the walls. Right now, there was nothing left to do but wait, as everyone who could be treated had already been taken care of. Sarah sighed and sat down, a feeling of tiredness taking ahold of her now that she knew she couldn’t do anything more to help. She leaned against the wall and let her head fall backwards, a feeling of dizziness taking over and her head pounding. She lifted her hand to her forehead, where blood was coming out when the explosion happened. There was still fresh blood on the wound but it was not bleeding too much; She refused to believe that it was something serious. Still, she felt a bit nauseous but blamed it on the lack a clean air rather than a mild head injury. Will, noticing that she looked a bit pale, crouched in front of her and she perked up, looking at his concerned features.

“You okay?” he asked motioning to her forehead.

“Yeah….” She sighed “I’m fine. Just hit my head during the explosion.” She shrugged as if it wasn’t a big deal.

“And you still ran around for the past couple of hours? Not checking if it was serious?” Will frowned. She felt like a child being scolded.

“You know I’m a doctor, right?” she chuckled quietly. “If it really was serious, I would have noticed. I just felt dizzy because I’ve been on my feet for hours that’s all”

The man in front of her rolled his eyes and got a small light out of his pocket, checking her eyes.

“You could have a concussion, seriously you…”

“Seriously I’m fine stop fussing over me” Sarah cut him off, a little annoyed. She hated when people treated her as if she were made out of glass, and she did not want to have someone taking care of her when so many were in worse shape that she was. Still, she let Will grab bandages and securing one on her forehead, where the wound was finally stopping to bleed.

The young brunette stood up with a sigh once he was done, aware that he was still looking at her carefully, when movement got their attention. Hermann had just gotten out of the room with Diane Claman and wore a solemn expression.

“What is it?” Matt Casey asked worriedly from behind the two doctors.

“Not contagious” Hermann told everyone, a grin breaking onto his face. Sarah’s eyes widened slightly, and she let out a breath she didn’t even know she was holding.

“Influenza A tested positive, but the Marburg virus didn't have time to incubate. Whatever he had in his body died with him.” Diane then said, her helmet off. The crowd cheered, people letting cries of joy and relief. Sarah turned to Will and the two shared a bone-breaking hug, laughing as a way to let out the stress.

“Open up the ER” Will called out and Otis who was close happily complied. Over his radio, Matt informed the chief that it was all clear and cheers could be heard outside. Sarah looked over at Gabby who was still siting with the older man, Jim. She approached them and gave Gabby a side hug before looking at Jim.

“Ready to pull that thing out and get out of here?” She asked with smile and the man nodded gratefully. The two women helped him sit on a wheelchair and watched as a nurse started guiding him towards another part of the hospital. Before he left, he latched onto Gabby’s arm, thanking her for everything. Gabby blushed slightly and brushed it off quickly, watching him leave.

“You know” Sarah said watching her with a smile. “I still remember when you wanted to become a doctor”

“I sure have gone a long way, haven’t I?” Gabby answered with the same small smile.

“Yeah you have.” Sarah chuckled and gave her another hug.

“You know we still all miss you at the firehouse… You sure you don’t want to come back?” she joked

“As much as I miss all of you, I guess I was always meant to be there.” Sarah sighed looking over her shoulder at the doctors and nurses of Chicago Med who were walking around helping people out. Gabby was about to say something else when a very worried Jay made his way towards his girlfriend. He took a few long steps and engulfed the girl into his arms. Gabby left quietly, not wanting to disturb the two as Sarah’s arms went around her lover’s torso, burying her face into his neck. As they broke the hug, Jay’s hand went to her face, his eyes widening slightly at the blood on her forehead.

“It’s nothing” she reassured him with a soft smile. “I’m fine I promise”. Jay let out a deep sigh looking her in the eyes to make sure she was telling the truth before nodding and taking her into his arms again. As they broke their second hug, Will put his hand on his brother’s shoulder, and Jay turned to him, giving him also a tight hug.

It took them a long time to actually transport everyone to different wings of the hospital. Every member of the staff that had been in the explosion had been dismissed, but none of them had actually left, helping around as much as they could. Once the day was over, and every patient had been looked after, Sarah tiredly walked into the resting room, only to find Hannah Tramble, sitting down on the ground, tears in her eyes, and Will’s hand placed on her knee in an attempt to comfort her. Sarah gave the two a week smile, sitting cross legged across from them.

“One hell of a first day huh?” she asked Will, although her tone made it clear that she wasn’t expecting an answer. It was a dark question to end a dark day.

Sarah had finally been able to go home and shower, to wash away the grime, dust and blood from the day. As she wiped the fog on her mirror, she took a look at her reflection. She looked pale, her skin contrasting with her dark brown hair, but also with the purple under her eyes. And on the top of her forehead, hidden among her hairline, there was a purple bruise, on which stood a red angry line. The young woman sighed before concealing her eye bags, applying a bit of makeup and going to her bedroom.

Jay sat on the edge of the bed, simply waiting for her to come out. He hadn’t really been able to talk to her since this morning, as both of them had been busy. He looked up as she entered the room, noticing the tired eyes of his girlfriend.

“We don’t have to go out, you know?” he said quietly “We could stay here and rest if you want to.”

“It’s fine” Sarah answered softly “Everyone is going out and I really need something normal today.” she explained.

Jay stood up and walked towards her, stopping only and inch from her. She could feel his breath as he looked at her, his hand slowly grabbing hers.

“I was so worried about you. When I heard, I hoped that you weren’t there. I just…” he struggled to find his next words, so he settled for simpler ones that he thought conveyed his feelings as best as possible. “I love you”

“I love you too” Sarah answered with a conviction in her eyes that made Jay smile. Jay’s hand rose towards her cheek, touching it as if she was the most precious thing in the world, before their lips connected, a way for them to express what their words couldn’t.

At Molly’s, the couple stood with their friends, beers in hand and laughing around when Chief Boden called for everyone’s attention. The room fell silent, looking at him as he spoke.

“Just a quick word.” He explained “Wanna take a moment and let you all get back to the fine cocktails that they serve here at Molly's.”

“Keep talking, Chief.” Hermann interrupted, which made everyone chuckle.

“To the good people at Chicago Med.” He said, raising his beer slightly. “You made us proud today. And we are very grateful for the service that you do for us and for the city. It's not said enough.” He told us, looking over at the different doctors, a small smile on his face.

“Thank you, Chief.” Sharon Goodwin answered for all of the staff that was here. “We want you all to know that every time those doors crash open, there are good people, strong people, people at the top of their game ready on the other side.”

With that being said, everyone raised their drinks, a distinct “hear, hear” to end and terrible day on a good note, surrounded by family.

Sarah leaned into Jay as they spoke to Brett, Mills and Will, and she stopped listening to the conversation for a minute, taking a moment to appreciate being surrounded by people she loved, and she smiled to herself, enjoying the beautiful moment she was living after a terrible day. She had hope that no matter how bad everything could get, she’d always get better.

#jay halstead #jay halstead imagine #jay halstead x reader #One Chicago #Chicago Fire #Chicago PD #chicago med #chicago pd imagine #chicago med imagine #one chicago imagine #OC #fanfic

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hwu-adventures-blog · 3 years

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All that Matters

Fic Description: Alicia Hardy and Ethan Ramsey’s relationship is complicated, it always has been, and after Alicia spends a night helping Ethan cook chicken, things start to be looking up for them getting together. However when death comes knocking at Alicia’s door, and they realise they might have just missed their chance...

Pairing: Ethan x MC (Alicia Hardy)

Taglist (please let me know if you to be added or taken off): @utterlyinevitable

First Chapter

Previous Chapter

Next Chapter

Chapter 5- Running Out of Time

An hour or so later and Alicia found herself and Raf surrounded by their friends, Jackie, Elijah and Sienna who had brought tea and cafeteria pizza for them, Bryce, having rushed down from Kyra’s surgery from this and even Aurora who had raced from Mass Kenmore after hearing about the news, all trying to cheer them up and comfort them. Some of the people she loved most in the world helping her and Raf through this, and although it would have been better with Ethan there as well, Alicia could help but selfishly think even though she knew he was working himself ragged with trying to find a diagnosis and helping in his own way by doing what he did best, the Pizza, was a welcome second place for a bonus, even if she didn’t feel like eating anything.

“Is there any news out there?” Raf asked from his bed he looked exhausted, his eyes sunken, dark bags visible under his eyes, he looked fragile with the breathing tube he was connected to through his nose. It broke her heart to see her friend like this all because of her stupid reckless actions. Alicia watched as Jackie and Sienna exchanged a long deciding look.

“What is it?” She asked

Sienna frowned

“Ethan and I managed to get access to Travis, and it helped us eliminate a lot more possibilities...but just as we were leaving, he died”

Oh no.

“But we’re closer to figuring out what this is!”

“Heads up” Elijah said surprised at the return of the diagnostics team in their hazmat suits, as they passed through the decontamination tent one by one, June, Baz and then Ethan, with Baz carrying a small blue cooler that Alicia somehow didn’t think was full of food or drink.

“We have something that should help you both” Ethan explained

“But not a cure”

Alicia felt a pang of disappointment, although she had not expected it to be a cure, maybe some part of her had hoped deep down it was and all of this would be over, Ethan glanced at her sympathetically and answered her statement, she could tell he hated seeing her like this.

“Not yet. But this should help alleviate some of the worst symptoms”

“Thank....you...” Raf said as Baz extracted two syringes from the cooler, Ethan took one and turning to Alicia, gently ushed her to the bed, not wanting anyone but himself to inject her Alicia suspected, not because he didn’t trust Baz or June but because he needed to make sure everything went right himself.

“You should sit” he said as a matter a fact rather than a suggestion, an gentle overall tone in his voice but with a authoritarian hint, knowing that Alicia, would have probably contested sitting down for the injection on any other day, in any other situation. However it wasn’t any other day or any other situation and she didn’t have the energy to argue with him and besides she was the patient now, and right got now, Ethan knew what was best so she easily conceded to his request.

“Just for a minute”

As she sat down on the bed, waiting for the needle to enter her skin, watching at the doctor, staring at the helpless look in his eyes behind the window of his helmet, wanting nothing more than to reassure him everything will be okay but knowing it wasn’t, her mouth suddenly started to feel as if it had gone dead, a painful prickling sort of sensation and Ethan’s face blurred in and out of focus, new symptoms.

“Alica...” his voice was calm, gentle, soft, as if he was pleading with her to tell him what was wrong, and Alicia realised something.

She now had a decision, she could tell Ethan the truth. The truth about how terrified she was of this whole situation, how petrified she was of losing anymore of her friends lives or even her own life because of a mistake she made, a rash decision she is now paying for, and have him reassure her that he was going to fix it again or tell her he won’t let her go. Or alternatively, she could report these new symptoms she was experiencing, as any bit of information, any new symptoms could or would help with the diagnosis. Admitting how scared she was, Alicia reasoned wouldn’t help anyone, so, purposely hiding away her feelings of terror, she opted to confirm to him what was important in that moment;

“I’m having paresthesia around my mouth and in my feet. And blurred vision”

“And any other developing symptoms?”

“I threw up a while back. But we all knew that was part of this, so I guess it’s not really a new symptom”

“.... I see. Thank you for telling me”

Ethan found a vein and pressed the syringe down, inserting the needle into her body, administering the treatment, it stung for a moment but that didn’t matter to her, it was insignificant compared to the pain she was going through in terms of seeing everyone else suffer because of her. Looking across the small room, to distract herself from that thought, she saw June pull out the other syringe from Raf’s arm as she felt Ethan do the same to her.

“Are the FBI going to autopsy the guy who did this?” Raf questioned, something which clearly caused Ethan’s expression of helplessness turn to something akin to frustration and anger.

“Yes, but they’ve informed me they have no intention of sharing those results with us. They’re claiming national security”

“Are you serious? That’s BS.” Elijah almost yelled from behind the window

“It is. But any petition to release it would take weeks, and we have hours. We need to work quickly to find a diagnosis”

“Especially since... since...” Elijah’s voice hitched, Jackie laid a hand gently on his shoulder before turning to Alicia.

“Danny is unresponsive. He’s going downhill fast”

“Oh my god...”

Alicia felt panic well up inside of her, no not Danny, they won’t let Danny die, they can’t can they? They’ll find out what’s wrong, they’ll find a cure in time, they have to! They won’t just-

“We’re not giving up on you... or Danny...” Sienna reassured her almost as if she read her mind and knew exactly what she was thinking.

“Between us and the diagnostics team, we have nine doctors working on this already. We should be able to solve anything” Jackie pointed out

“I’m just a surgeon, but I’ll offer whatever help I can” Bryce stated and Alicia managed a smile

“This isn’t time for that confidence of yours to do a runner, Bryce”

“Yeah you’re not just anything” Sienna added

“Sorry. I mean, we’ve got this!” Bryce grinned

“So here’s where we are.” June changed the subject, Alicia had almost forgotten the diagnostics team was there, even though it was damn near impossible to completely forget that fact. “we’ve ruled out Anthrax, Botulinum, Ricin, Tularemia, and we’re waiting on results for Tabun”

“And the FBI have ruled out half a dozen fungal toxins, Ebola, Marburg’s, and all the Novichok nerve agents” Ethan continued, calmly and professionally although Alicia could tell he was at least a bit worried about the lack of positive results as he looked at her, not tearing his gaze away for a second

“That’s a pretty broad field” Jackie raised her eyebrows

“When you have so little to go on, you need to cast a wide net” Baz pointed out

Alicia watched as Ethan regained his focus, noting Baz’s sad expression

“Still, it’s progress. The fact there’s still no fever means it’s almost certainly not a bacteria or a virus. We’re shifting our focus to-“

Raf groaned in pain, June stopped dead as he clutched his chest and lurched violently sideways, getting up from the bed in one swift motion Alicia raced towards Raf to catch him before he toppled to the floor.

“Raf!” She heard Elijah say from outside.

“It’s alright, he just fainted” she reassured her friends, but couldn’t help but be concerned for what this could mean, she leaned Raf back against the soft pillow. And after a few seconds he opened his eyes again, coming back around, blinking confusedly.

“....what does this mean?” Aurora asked Ethan frowned in response, that mixture of concern and helplessness visible behind the window of his helmet once more, mirroring Alicia’s exact expression and feelings in that moment.

“....means we need to move even faster than we thought.”

#mc x ethan #ethan x mc #pixelberry #playchoices #mc #ethan ramsey #ethan ramsey x mc #choices: open heart #open heart second year #open heart second year spoilers #open heart spoilers #open heart

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goldkirk · 4 years

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1. that was a REALLY good chapter i cried like through all of it 2. if you dont mind, how does ebola work? how does it progress through the body, and how do the current treatments we have work against it?

HI FRIEND HOLY MOLY AAAAAAH

1) omg I am so sorry for the tears but THANK YOU I’m so glad you liked it!!!!

2) OH BOY I AM SO EXCITED TO EXPLAIN, THIS IS ONE OF MY FAVE TOPICS AAAH

okay so first, I have an ENTIRE post about Ebola, its history, and cross-species jumps HERE that is (in my own biased opinion) a good read and what you should hop over to before reading any further in this post

SECOND, here is a post where I break down all the mcfreakin Mistakes the comics did when they had Tim get “Ebola” in contagion and what should have happened instead

and the tl;dr: Ebola is a Really Godawful virus that is as bad as it gets, in the same category as Marburg and Smallpox and Lassa Fever, et. al., and the main strain that affects humans has had, up till the past few years, a 50-90% fatality rate. Holy shit.

It cropped up for the first time in the 70s, making a cross-species jump from (we’re pretty sure) bats to humans in Africa, and had a few smaller outbreaks after that until finally having a major one in 2014 that rocked the world and decimated entire areas of West Africa.

Ebola, unlike more focused viruses, targets every type of tissue in the human body pretty much, aside from bone and skeletal muscle. It has a very special love for blood vessel cells, in particular, which is what leads to the characteristic hemorrhaging that people associate with Ebola (but which doesn’t always happen on a catastrophic scale in all patients). Blood vessels become weak and spontaneously break, leading to a rash-like pattern on peoples’ bodies. The eyes can be red. People get very high fevers, headaches, lots of pain in some cases, and when things are turning fatal, they can develop fatal brain swelling and catastrophic hemorrhaging in several areas of the body. A major problem is that Ebola makes your tissues just…literally turn into liquid slimy soup, basically, as it turns cells into replication machines and then busts them open and kills them. It attacks the spleen and liver first, and then gets a giant foothold in your body from there. And, uh, the entire gastrointestinal tract is a major casualty of this process, and basically starts to just…die inside itself…and liquefy into a bloody soupy mess…and people throw up blood and hemorrhage through bloody diarrhea and it’s just really awful and terrible and yeah Ebola liquefies you. That’s. That’s the simplest way to put it. It turns you into a virus-making machine, liquefies you, and even your sweat contains millions of particles of the virus in just a droplet or two. It only takes 1-5 particles to infect and kill a person, so…yeah. Ebola is terrifying and HORRIFICALLY contagious just because people are spewing fluids AND sweating from fever ANd also just have tears and sweat in the first place bc they’re human.

HOWEVER. The one advantage we have is that people are NOT symptomatic until they show symptoms–which is generally breaking with a fever and getting a headache, and is followed by increasing symptoms over the following days.

BUT!!!! BUT!!!!!!!! Some really fucking amazing people have been working for decades on treatments and a vaccine, and during the 2014 outbreak this new revolutionary antibody drug called ZMapp saved several peoples’ lives, and then a couple drugs were made modeled off the same principle of that one, and we now have a drug that in the most recent 2018 Congo outbreak of Ebola was tested and found to have an even better success rate (read about it here) and THEN in EVEN BETTER NEWS the FDA APPROVED A VACCINE FOR THE VERY WORST EBOLA STRAIN, ZAIRE EBOLA, AND THAT IS SO EXCITING AND AWESOME.

IT’S CALLED ERVEBO AND IT HAD AND 97.5% SUCCESS RATE IN A STATISTICALLY SIGNIFICANT SAMPLE SIZE OF ~15,000 PEOPLE AND I AM STILL HYPED EVEN THOUGH IT’S BEEN MONTHS!!!!!!

FUCK YEAH SCIENCE I LOVE HUMANS WE LOOK DEATH IN THE EYE AND SAY NOT TODAY AND NOW WE HAVE AN EBOLA VACCINE AND AREN’T GIVING EBOLA MANY CHANCES TO MUTATE INTO SOMETHING WORSE ANYMORE. TAKE THAT, EBOLA!!!!!!!!

#hope this answers your question!!!!! i'm so happy to yell literally anytime #makiharukawa #katie answers asks

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rudrjobdesk · 2 years

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कोरोना के बाद चमगादड़ से फैलने वाले इस खतरनाक वायरस ने दी दस्तक, जानें लक्षण

Image Source : REPRESENTATIVE PICTURE Corona And Marburg Virus Highlights पश्चिमी अफ्रीका में मारबर्ग वायरस ने दी दस्तक, 2 की मौत WHO ने इस नए वायरस को लेकर चेतावनी जारी की भारत में बीते 24 घंटे में कोरोना के 18,840 नए मामले Corona And Marburg Virus: देश में कोरोना की रफ्तार एक बार फिर तेज होने लगी है और 24 घंटे में 18 हजार से ज्यादा मामले सामने आए हैं, वहीं दूसरी तरफ पश्चिमी अफ्रीका में नए…

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khartoumnews · 1 year

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sbgridconsortium · 6 years

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Hiding in Plain Sight

Gaya Amarasinghe Washington University in St. Louis

On a recent visit to the laboratory where he worked as an undergraduate, Gaya Amarasinghe thought about his scientific journey from student to professor. At first glance, his research interests seem to have drastically changed. Back then, he was studying signaling in cancer biology, and how oncogenes communicate within cells. Now, his group at Washington University in St. Louis investigates how some of the world’s deadliest viruses, such as Ebola, outcompete the host and cause disease.

Yet, he decided, not much has changed after all. “In the last 20 years, I haven’t done anything differently,” joked Amarasinghe, who trained as a structural biologist and biochemist. “My group now studies proteins from viruses and bacteria, but they interact with and sometimes hijack the same immune signaling cascades I studied before. I’m asking the same questions.”

Amarasinghe’s group examines how the host immune system recognizes foreign pathogens and how normal immune signaling changes in the presence of microbes.

“We ask simple questions, and we answer them using simple experiments,” Amarasinghe says. “What are the initial components in the system, what does the structure look like, and what are the dynamics of these molecules? Then we ask what happens to those properties when they interact with a virus. What does that interaction look like? How does it move? What changes?”

It was a question that first made them curious about Ebola and related Marburg viruses: How do they evade the pathogen detection system that the immune system uses to distinguish self from non-self?

Most people know these filoviruses as causes of severe, often fatal, outbreaks of hemorrhagic illness, usually in Africa, where people first catch the contagious diseases from animals.

Few viruses are as dependent upon first interactions with the host as Ebola and its cousins. Unlike other viruses with multiple ways of manipulating an immune response during an infection, Ebola and Marburg viruses begin with a knock-out punch to the immune system defenses. It happens at the earliest stage, Amarasinghe says.

The critical moment comes when the innate immune cells that function as sentinel cells in the host, such as dendritic cells and macrophages, recognize the viruses as unwanted foreign invaders—or not, as is often the case.

A key player is a crucial viral protein called VP35. Without a working VP35, the viruses cannot defend early immune responses during infection. It also blocks many steps of the host’s innate immune response, including one that ramps up the antiviral immune fight.

The first attempts to answer the question about initial recognition of the virus were anything but simple. “The hardest part was getting the material we needed,” Amarasinghe says. It was a brute force effort to purify the protein. He estimates it took the equivalent of 10-20 people-years of work in many groups, including his own, to finally isolate well-behaved VP35 by genetic recombination techniques.

In 2009, his group published the first of a half-dozen papers, which include at least 10 different VP35 structures of what the interferon inhibitory domain (or IID) from several Ebola strains and Marburg, which have different disease courses.

“VP35 IID was nothing like anyone predicted,” Amarasinghe says. “This protein is hiding the non-self signal that would otherwise get recognized by the immune system. It’s hiding the signal in plain sight.” The protein doesn’t even need to move much. It has a fold that fits neatly over the non-self signal, an end of the detection RNA found in every cell.

The group also found a fundamental difference between Ebola and Marburg viruses in how they recognize the host RNA and hide it. “They are equally virulent and pathogenic, but there is a key difference at an early stage,” he says. “Why does that matter? What happens in early stages determines the outcome of infections.” For example, Reston Ebola virus, a close cousin of the more virulent filoviruses also uses VP35 to bind RNA, but differences in other parts of the virus replication cycle make Reston non-pathogenic in humans.

Once they knew what the protein looked like in the related hemorrhagic viruses, Amarasinghe’s team helped design mutated versions to model the disease and better define the biology. The mutated viruses were immunogenic.

“Very cool, because now we have virulent and avirulent near-isogenic viruses to study the disease in animal models” he says. This knowledge can be used to develop actual vaccine candidates with different molecular backbones or using smaller subunits for safety, he says.

Most of the lab’s work happens in test tubes with non-infectious viral proteins. “We have collaborators working in biosafety level 4 that put some of these crazy ideas to work,” he says. Amarasinghe and his collaborators are testing the biological mechanisms in animal models.

A second set of discoveries from their work helps explain why Ebola and Marburg are not responsive to interferon, a potential treatment given for many viral infections, but as it turns out it does not work well in filoviral infections. VP24, another protein encoded by the Ebola virus binds to a key cargo transporter called karyopherin, which is responsible for moving important signals, or transcription factors, into the nucleus to trigger an immune response. Viruses are known to block dendritic cells from maturing, preventing the normal interferon signaling necessary for an adaptive immune response. Amarasinghe and his colleagues have shown that VP24 also inhibits molecular signaling from therapeutically delivered interferon.

“Typically we think of a host-microbe arms race, with the host evolving away from the pathogen,” Amarasinghe says. “In this case, the place where the viral protein binds is unable to evolve away, because the host would become non responsive to its own immune signal. The virus identified an area where mutation change rate is low.”

Most of the lab projects fall into one of two categories—how host factors recognize the signature or foreign pathogens, and how host signaling changes in the presence of a microbe.

The host stress response to a virus, and not the virus itself, could be responsible for some diseases and point the way to better treatments. This could be the case with the human respiratory syncytial virus (hRSV), an infection most kids acquire by age 2. It can be fatal to infants and the elderly. It is in the same family as another emerging infectious disease people catch from animals is Nipah virus, an often fatal infection that causes encephalitis and severe respiratory distress.

Amarasinghe and his colleagues purified and solved the first crystal structure of an hRSV protein known as NS1. They reported their findings in 2017 in Nature Microbiology. They found a duplicated structural fold that suggests NS1 may have a greater role in regulating host responses than previously appreciated. “It’s not quite falling off log, but it’s close,” he says about the functional revelations.

In the future, Amarasinghe says his lab will continue to explore what drives infection in the early stages from host response point of view, aiming to understand factors that determine outcome in longer term persistent infections. The knowledge may be useful in other bacterial and viral systems, including the effect of co-infections on outcomes. “None of these exist in isolation,” he says.

Amarasinghe starts many days as early as 4:00 am and most mornings with a long run or a bike ride. It keeps him in shape for occasional long-distance mountain biking or skiing.

By his name alone, Amarasinghe may have been destined to work with proteins and RNA. Every letter in his full name represents an amino acid. He pointed out that his first name, GAYA, also forms a tetraloop (guanine-adenine-pYrimidine-adenine).

-Carol Cruzan Morton

#sbgrid #member tale #biomedical research #science #nature #biology #structural biology #immunology #ebola

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bnfbc · 2 years

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Vaccinated - by Paul A. Offit - October 2021 - selected by Dave

Andy: “Great discussion. Learned some things.” C+

Gabe: “This was one of those books where the discussion was far superior to the book itself. While I appreciated the author's attempt to tell a forgotten story, I found his writing style very clunky and disjointed. He also was pretty dismissive of concerns about vaccinations or their development, which I found off-putting. Nevertheless, the conversation it sparked was fantastic, so I appreciate it for that as well.” D

Jachles: “Considering the times that we were living in while reading this book, it was really interesting to read. There was a section about the possible implications of future pandemics that was a shockingly accurate description of the COVID pandemic despite being written 10 years earlier, and even a reference to Dr. Fauci (referred to as “Tony”). Pretty cool that we’re still using the Mumps vaccine strain that Maurice Hilleman created from his daughter’s Mumps virus back in the 60′s. I wish there had been more discussion of the ethical implications of how vaccines were first created. Lastly, there were a few good connections to previous books, including a references to Marburg (The Hot Zone) and William Jennings Bryan. Shoutout to Marburg. The virus of course. Not Germany.” B+

Paul: “One man is responsible for eight of the vaccines that are currently administered to most Americans. You’d think this man would be more well-known. You’d definitely think I would at least remember his name a mere month and a half after reading this book. But no, I just had to Google Maurice Hilleman, because despite the best efforts of Paul Offit, something about Hilleman remains elusive. And in reading this book you get the sense that Hilleman himself probably wouldn’t mind. He’s painted as a gruff, single-minded curmudgeon, who had no interest in the spotlight and just wanted to make vaccines dammit. So while the biographical component of this book was a little ‘meh,’ Offit does an excellent job in tracing the history and scientific advances in vaccine technology from their origins to the present day. The science writing is clear and crisp, and I particularly appreciated the section about the rise of the anti-vax movement. This book was written well before the COVID pandemic but helped bring to light just how world-changing vaccines have been, while also illuminating some of the root causes behind the misinformation about vaccines that’s sadly so prevalent today.” B+

Tommy: "Maurice Hilleman was involved with the creation of vaccines for measles, mumps, rubella, Hib, and hepatitis B, but is mostly unknown. Offit theorizes that Hilleman's relative anonymity is due to both his modesty and working on the corporate side of vaccinology versus being a scientist in academia. Despite the book's subtitle, the picture of Hilleman remains opaque. Offit tends to introduce characters quickly with brief descriptions and squeezes in a few entertaining anecdotes, but doesn't leave the reader with many lasting impressions. The science of vaccinology was detailed throughout, but it remained mostly surface level. The sections that hooked me in explained why the vaccines worked, like growing in animals weakens the virus's ability to grow in humans or growing the virus at lower temperatures in fetal cells decreases their survival at higher temperatures. An important question raised in the book centered around the ethics of testing vaccines, but again the reader wasn't provided with enough details to gain a deep understanding. The book would have greatly benefitted from deeper dives on the thinking and experimentation undertaken by the scientists, especially Hilleman." C+

GPA: 2.27

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isiso8 · 3 years

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The Marburg plan they have for us is even scarier than all they've done to us under the name of Covid 😧

BitChute (https://www.bitchute.com/video/K9tj9HXBDM9l/)

Covid-19 May Have Just Been A Trial Run: Kieran Morrissey Explains The Worrying Marburg Virus

Gates of Hell and the World Health Organisation may have something far deadlier and horrific in store for all of us - the Marbu https://www.bitchute.com/video/K9tj9HXBDM9l/

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aion-rsa · 3 years

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Riverdale Season 5 Episode 11 Review – Chapter 87: Strange Bedfellows

https://ift.tt/eA8V8J

This Riverdale review contains spoilers.

Riverdale Season 5 Episode 11

“What the hell just happened?”

Following a lengthy hiatus, Riverdale has finally returned with its final batch of episodes from the series’ fifth season. As you may or may not recall, when credits rolled on the previous episode Riverdale High was being destroyed by convicts freed by Mr. Lodge from his prison, Veronica had retreated to New York City, and, most excitingly, Jughead was apparently abducted by aliens (which, in this show’s universe, would be a pretty ordinary development).

Unfortunately, this latest installment quickly undoes these game-changing developments in the lamest television backpedal since Millennium transformed the supposedly world-ending Marburg Virus into a regional outbreak. (Oh how one yearns for an era when global pandemics were the stuff of pop culture fodder). Thusly, Riverdale High can be back up and running in three weeks, Veronica is back in Riverdale, and Jughead’s abduction was explained as a bad Maple Mushroom trip. It is this last development that is most disappointing as this season has been hinting at otherworldly activity such as aliens and Mothmen constantly. So now are these paranormal plotlines gone, or is this episode merely a red herring until the weird shit returns? Hopefully the latter, otherwise Riverdale has once again succeeded in spinning its wheels with a mystery that never fully satisfied. (The Farm, I’m talking about you).

Speaking of The Farm, Riverdale is going back to the crazy religion well again with the Blossoms’ new Jason-themed cult. Cool though it may be to dream of, as Penelope puts it, “a realm beyond this mortal coil where maple syrup flows in rivers,” we have already seen this exact storyline before. So unless the writers are planning on making up for the Farm’s petering out by harnessing the unhinged power of the Blossoms’ insanity, this plot may just be another exercise in futility.

Arguably the biggest reveal of this episode is that we learn that the real estate Mr. Lodge bought up in the town formerly known as Riverdale is rich with palladium, and his goal to destroy the community so that it can bleed its natural resources dry comes sharply into focus. Well, at least somewhat into focus. Lodge has been playing the long game here, and while this particular installment doesn’t make too huge of a deal about his scheming, it is nice to know there’s some actual motive behind his actions other than inconsistent characterization.

This leads us to Archie and company’s rescue of Governor Dooley and their most recent defeat of the Dickinson clan. There was little doubt that our heroes would save the day, so what could have been some rote storytelling was leveled up with the best fight choreography seen on Riverdale to date. More of this please.

The best part of this episode? Establishing the friendship between Tabitha Tate and Betty. Erinn Westbrook and Lili Reinhart shine in their scenes together, and their trip sequence was a comedic highlight. I’ve stated many times before that the true pleasure of Riverdale is how ridiculous it is, so it is a challenge to deliver ridiculous dialogue and sell the insane plots in a believable fashion without winking at the audience. Westbrook and Reinhart’s performances here show that as dumb as things get, they still are handled skillfully in a way that heightens the entertainment.

As the episode ends, Jughead finds himself getting into the truck of what appears to be this season’s Big Bad while one his way to resolve his mystery NYC trauma. I don’t know what will happen next, but I’m still holding out hope that somehow, some way Mothmen are involved…

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Riverdale Roundup

Yes, we live in an era of corporate synergy, but it is still weird seeing Jughead, an Archie Comics character, wearing a Superman T-shirt.

If Cheryl is still keeping Jason’s skeleton around, who did she give the Viking funeral to?

Having the psychedelic “Walking in Space” from the Hair soundtrack Betty and Tabitha’s trip/the hostage rescue/Penelope and Cheryl’s current descent into madness was some inspired musical direction.

In this episode, Betty — an FBI agent — is effortlessly drugged by an NYC burnout. Even for Riverdale this is an absolute contrivance.

What does Vanessa really want with Jughead’s manuscript? Is there more to her alleged motive that to see if Jug wrote about their volatile time in NYC together?

Veronica mentions her outfit is from Lacy’s new fall line, in this show’s latest nod to the gone-too-soon Katy Keene.

For those of you who, like I was, wondering what the hell Palladium is, Wikipedia comes to the assist.

K.J. Apa’s hair dye was working overtime in this episode.

In an episode sprinkled with tidbits filling in backstory that happened during the time gap, the most interesting revelation is that Reggie began working for Mr. Lodge after his father borrowed money from him.

As far as Veronica knew, Tom Keller was bleeding out on the floor of the El Royale. Not that she even thought to mention that to Kevin or Archie or anyone really.

Alice quips “back to remote learning” after discovering that Riverdale High will be out of commission for three weeks. Did the pandemic happen in the show’s world?

“Although this may be potentially cringey, I think we should read Jughead’s manuscript,” says Betty, in the episode’s most truthful line.

Has this series ever had a less compelling B-plot than Jughead’s Sketch Alley walkabout? No. No it has not.

The post Riverdale Season 5 Episode 11 Review – Chapter 87: Strange Bedfellows appeared first on Den of Geek.

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bbcbreakingnews · 3 years

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What is Disease X? Scientists who discovered Ebola warns against potentially fatal viruses

NEW DELHI: The scientists who helped discover the Ebola virus in 1976 has warned against an unknown number of new and potentially fatal viruses faced by humanity among which is ‘Disease X‘. “We are now in a world where new pathogens will come out,” said Professor Jean-Jacques Muyembe Tamfum, who helped discover the Ebola virus in 1976, adding, “And that’s what constitutes a threat for humanity.” Muyembe’s statement comes on the heels of a patient being infected by a pathogen that has not yet been identified but had symptoms similar to Ebola. In a remote town in the Democratic Republic of the Congo (DRC), last month a woman showed early signs of hemorrhagic fever. Her samples were tested for Ebola and other diseases with similar symptoms. All came back negative making the disease which affected the woman a mystery. Scientists speculated if she could be the patient zero of “Disease X” the first known infection of a new pathogen that, researchers say could be more contagious than the Covid-19 and with Ebola’s 50 per cent to 90 per cent fatality rate. In 2018, the World Health Organisation (WHO) published its global plan for accelerating research and development during health emergencies and also included “Disease X” in its ‘2018 R&D Blueprint’. The 2018 R&D Blueprint prioritized nine diseases for R&D which consists of Covid-19, Crimean-Congo haemorrhagic fever, Ebola virus disease and Marburg virus disease, Lassa fever, Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS), Nipah and henipaviral disease, Rift Valley fever, Zika and the latest addition “Disease X”. All these diseases lack an effective drug or vaccine. What is Disease X? “X” stands for unexpected, explained Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases. WHO said that it “represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease.” As of now, Disease X remains hypothetical, an outbreak that scientists and public health experts fear could lead to serious disease around the world if and when it occurs. Speaking to CNN, Muyembe warned of many more zoonotic diseases — those that jump from animals to humans — to come. Zoonotic diseases like yellow fever, rabies, brucellosis and Lyme disease spread from animals to human beings and have caused epidemics and pandemics before. While the deadly HIV emerged from a type of Chimpanzee and then mutated into a fatal disease, SARS-CoV-2, along with SARS, and MERS are all coronaviruses that have suddenly jumped from animals to humans. (With inputs from agencies)

source https://bbcbreakingnews.com/2021/01/05/what-is-disease-x-scientists-who-discovered-ebola-warns-against-potentially-fatal-viruses/

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liliannorman · 4 years

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How to find the next pandemic virus before it finds us

More than 100 years ago, a deadly flu virus circled the globe. It caused the influenza pandemic of 1918-1919. Before it was over, this disease had sickened an estimated 500 million people. That was one-third of everyone alive at that time. Some 20 million to 50 million people died.

Flash forward to the 1970s. People in a small Central Africa village fell ill with a mystery disease. It caused bleeding that would not stop. Soon, this Ebola virus would spread to other villages.

Explainer: What is a coronavirus?

What do these famous viral outbreaks have in common with the new coronavirus disease known as COVID-19? Scientists believe animals initially carried the viruses that cause all three. Such diseases are known as zoonoses (ZOH-wuh-NO-sees). That means they started in animals and later spread to people.

Flu likely came from birds. Researchers think that bats may have been the source of the Ebola virus and of COVID-19. “Roughly 75 percent of global pandemics and disease outbreaks caused by new viruses come from wild animals,” says Tracey Goldstein. She’s a virus detective at the University of California, Davis. She hunts for new viruses among the wild animals of Africa.

When viruses pass from wildlife to people, it’s called a spillover. Fortunately, spillovers that affect more than a handful of people are rare. But big spillovers do seem to be happening more often, Goldstein and others observe.

To prevent the next big outbreak, researchers around the world are scouting the role of wild animals in the emergence of new human diseases. Scientists want to understand which groups of animals or viruses pose the biggest risks. What they learn could help us all.

Virus hunters turn to bats

Viruses are tiny, infectious particles. They “live” but aren’t technically alive. They can reproduce only within the cells of a living host. That host can be an animal, plant, bacterium or fungus.

“Humans carry lots of viruses,” notes biologist Kevin Olival. He works for a group called the EcoHealth Alliance. Based in New York City, it tries to protect people and wildlife from new diseases. Measles and common skin warts are examples of viral diseases. But not all viruses are harmful, Olival notes. Some seem to have no effect on the body. It all depends on the virus and the host.

Scientists Say: Outbreak, Epidemic and Pandemic

“All mammals carry viruses,” Olival says. “But there’s something about bats that might be a little different or unique.” That’s why he has made bats — and the viruses they carry — a focus of his research.

Bats are thought to be the host for a number of relatively new viruses that can sicken people. Among them are the Ebola virus, Marburg virus, Nipah virus and SARS-CoV-2. That last one is the coronavirus responsible for COVID-19. In 2002, another coronavirus from bats caused a massive outbreak of SARS (severe acute respiratory syndrome) in China. Highly contagious, SARS showed some similarities to COVID-19.

Olival and his colleagues at EcoHealth Alliance have been studying the coronaviruses hosted by bats. In China alone, they found 400 different strains of these viruses. Most of them probably wouldn’t sicken people, he says. To figure out which can, researchers will have to perform tests. That will involve taking human cells and infecting them with each virus in the lab, he explains.

See all our coverage of the new coronovirus outbreak

Or, researchers could survey people living near the bats and sample their blood. Olival’s colleagues at EcoHealth Alliance were part of a research team that did just that. They worked in rural Chinese villages. And there they found signs that mini coronavirus spillovers have been underway.

The researchers surveyed 1,585 people. They collected blood from 1,497 of them. Of these, 265 (almost one in every six people) reported some symptoms in the past year of a SARS- or flu-like disease. Nine people also tested positive for SARS-like coronaviruses that had previously been found in area bats. None of these nine remembered having any interactions with bats. However, the people who had reported SARS-like or other severe respiratory infections did say they had been exposed to wildlife and livestock.

This suggests that there may be zoonotic illness in these populations. And, the researchers add, the novel bat-linked viruses in the blood of some of these villagers offers “evidence for bat-borne coronavirus transmission to people.” Hongying Li of the EcoHealth Alliance and her colleagues reported their findings in the September 2019 Biosafety and Health.

Why bats?

Researchers don’t know precisely why bats are a good host for many deadly viruses. But they have some ideas. Bats are the only mammals that fly. (Other “flying” mammals don’t fly. They only glide.) Flying is hard work. A bat needs about twice as much energy for its flight muscles as a similar-sized rodent needs to run on the ground. Putting all their energy into flying could leave bats with less energy to fight off sickness or injury. But that doesn’t happen. Scientists think that flight may have led bats to evolve stronger immune systems than other mammals.

Judilee Marrow collects a saliva sample from a rodent in Gabon, Africa. She and her colleagues at Smithsonian’s National Zoo take these samples to the lab where they will be investigated for viruses.C. Whittier

A unique immune system might mean a unique response to viruses. For instance, one recent study showed that bats’ bodies can limit the ability of a virus to trigger dangerous inflammation. That response may push viruses to evolve in ways that let them rapidly spread from cell to cell. And if that altered virus now spreads to a species without such a strong immune system, the new victim might get super-sick — and quickly.

Olival’s work has mainly taken him to Malaysia. This Southeast Asian nation has more than 100 bat species. He wants to better understand how viruses there might spread between different groups of bats. So he collects genetic information from bats and bat viruses. He uses that to build computer models. These computer programs predict which bat viruses could cause real harm in people and other animals, he explains.

Explainer: What is a computer model?

Some, such as the Nipah virus, can infect a wide range of animals. Several species of fruit bats in Southeast Asia carry that virus without getting sick. But in 1999, Nipah virus triggered a deadly outbreak among Malaysia’s pigs and pig farmers.

Goldstein’s team performed similar work with bats in Sierra Leone. That’s a country in West Africa. Her group had suspected local bats carried the Ebola virus. It was not a wild guess. In 2014 and 2015, an Ebola outbreak killed nearly 4,000 West Africans. And in January 2015, researchers linked the start of that outbreak to a two-year old boy in Guinea. He liked to play in a hollow tree where insect-eating bats used to live.

Scientists perform lab work in Tanzania to look for new viruses from wild animals.USAID PREDICT

Villagers had burned the tree down. But insect-eating bats had been linked to earlier Ebola outbreaks. That made these animals the most likely suspects in the West African outbreak, explained Fabian Leendertz at the time. He works at the Robert Koch Institute in Berlin, Germany. His team described how its detective work led to this conclusion in the January 2015 EMBO Molecular Medicine.

“We wanted to see what other viruses were circulating in bats and other animals” in Sierra Leone, recalls Goldstein. That country shares a border with Guinea. Knowing what viruses the bats hosted might help researchers better understand their viral risks to people.

The bats in Sierra Leone carried Marburg virus, Goldstein’s team discovered. It’s a close relative to the Ebola virus. Marburg causes severe bleeding in people, just as Ebola does. But Marburg has not yet sickened anyone in Sierra Leone. The researchers found the disease in bats before any people got sick. But now Goldstein’s group knows that bats pose a Marburg risk there.

Protecting people and wildlife

Figuring out where potentially dangerous viruses come from is only part of the challenge. Research also needs to identify what activities put people at risk of exposure to animal viruses, note Goldstein and Olival.

These new viral diseases aren’t passing from wild animals to people because animals are going out of their way to mess with us. “It’s because we interfere with them,” says David Quammen. He’s a science journalist. And he researched the topic for a book he wrote eight years ago, Spillover: Animal Infections and the Next Human Pandemic.

Ecology is a branch of biology that explains how different living things interact with each other and their surroundings. And “humans are changing ecology,” observes Hellen Amuguni. She’s a veterinarian and infectious-disease researcher at Tufts University in North Grafton, Mass. People can alter ecology by cutting down trees in forests. Or they might build roads or cities through the landscape. Some might hunt down wild animals for pets or food, explains Amuguni. All of these activities can impact the local ecology in ways that scientists are just beginning to understand.

One new study backs that up. Christine K. Johnson of UC Davis and her colleagues published it April 8 in the Proceedings of the Royal Society B. They found that hunting, wildlife trade, habitat destruction and the spread of cities into areas that were previously wildlands all increase the risk of virus spillovers. Selling wild animals at markets or shrinking their natural habitat can jumble together species that wouldn’t normally meet.

Hongying Li visits a live-animal food market in China. All animals, including these, may harbor harmful viruses. Li’s team is surveying the types of wildlife and livestock that local consumers might encounter.EcoHealth Alliance

Scientists think that the new coronavirus might have come from a live animal market in China. The virus could have passed directly from a bat to a human. Or it could have passed from a bat to another animal that was touched by a human. Wild animals kept in cages come into close contact with people and other animals. That provides more chances for viruses to spill over from one species to another.

And these events can be just as bad for wildlife as for people, points out Christopher Whittier. He’s a veterinarian at Tufts who studies human diseases that spill over into wildlife. “Understanding what viruses are in wildlife can help us to protect wild animals, too,” he notes.

The human measles virus can sicken and even kill mountain gorillas. Researchers in Africa discovered this back in 1988. People would gather to watch the apes in Rwanda’s national parks. At the time, no one knew that someone’s sneeze can infect local primates with colds and other viral diseases. And there’s plenty of opportunity for that. Each year, park gorillas and chimps were exposed to more people — and their germs — than would visit the average person’s house over a lifetime.

After scientists realized that these wild animals could get sick, practices changed. Today, people visiting wildlife parks in Africa are asked to keep at least 7 meters (23 feet) away from apes to avoid spreading germs.

When you really think about it, human health, animal health and the environment are all connected, says Olival. Preventing the next pandemic will take the work of doctors, veterinarians and scientists. Each field contributes something different to the understanding of new zoonotic diseases. “If we all come together,” he says, “we can improve the health of humans and the planet.”

Chris Whittier and his colleagues in the Central African Republic collect blood and saliva samples from this western lowland gorilla. These great apes can become infected with human viruses, including measles. The researchers’ goal is to protect gorillas, such as this adult female, from human viruses. This sedated animal will be released once she wakes up. C. Whittier/WWF

How to find the next pandemic virus before it finds us published first on https://triviaqaweb.tumblr.com/

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scienceblogtumbler · 4 years

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COVID-19 Relies on Cell’s ‘Master Regulators’ for Survival

UC San Francisco scientists assembled an international research team that has figured out how SARS-CoV-2, the virus that causes COVID-19, hijacks proteins in host cells that serve as master regulators of key cellular processes. By doing so, the virus is able to rewire the cell’s internal circuitry to promote its own spread and survival. But the reliance of the virus on host-cell proteins may also prove to be its Achilles’ heel, as these same proteins can be easily targeted with existing drugs.

In a study published June 28, 2020, in Cell, the researchers found that when SARS-CoV-2 infects cells, it assumes control over a family of enzymes known as kinases. Under normal circumstances, kinases serve as master regulators of metabolism, growth, movement, repair and other important cellular functions. Kinases work by attaching tiny chemical tags to proteins through a process known as phosphorylation. Once attached, these tags act as switches that turn proteins on or off, which keeps the complex machinery of the cell running smoothly.

When a cell is commandeered by SARS-CoV-2, however, these same kinases behave in ways that disrupt normal cell function and transform the host cell into a virus factory. Cell division comes to a halt, inflammation pathways are activated, and the cell even begins to produce tentacle-like structures known as filopodia, which protrude from the cell’s surface and may serve as molecular highways that help the virus spread rapidly to neighboring cells.

These new findings build upon a widely cited paper published in April that was among the first to map out the many ways in which SARS-CoV-2 interacts with the proteins it encounters when it infects a cell. That study also identified a number of existing drugs that were able to block these interactions, making them attractive candidates for use as therapeutics against COVID-19.

Both efforts were spearheaded by the UCSF’s Quantitative Biosciences Institute (QBI). Soon after COVID-19 emerged as a threat to global health, QBI Director Nevan Krogan, PhD, assembled a crew comprised of dozens of UCSF scientists representing a broad range of scientific disciplines in an effort to address the pandemic from as many perspectives as possible. The QBI Coronavirus Research Group (QCRG), as the cross-disciplinary team is now known, includes a number of scientists with expertise in kinases, as well as the drugs that can be used to disable them.

Kinases and the signaling pathways they control have been the subject of intense scientific scrutiny for decades, in no small part because abnormal kinase activity is frequently implicated in cancer. Over the years, this has led scientists to develop dozens of drugs that target these enzymes – drugs originally intended as cancer therapies, but which could potentially be used to hobble kinase-dependent viruses like SARS-CoV-2.

This dependence of SARS-CoV-2 on kinases was revealed in experiments in which the researchers counted and catalogued all the proteins found in both infected and uninfected cells. Though they observed no significant differences in the total amount of protein found in each group, the scientists noticed huge disparities in phosphorylation levels – a clear sign that SARS-CoV-2 was changing kinase behavior in infected cells.

“By conducting a systematic analysis of the changes in phosphorylation when SARS-CoV-2 infects a cell, we identified several key factors that will inform not only the next areas of biological study but also treatments that may be repurposed to treat patients with COVID-19,” said Krogan, a professor of cellular and molecular pharmacology at UCSF, a senior investigator at Gladstone Institutes and co-senior author of the new study.

Further analysis by first author Mehdi Bouhaddou, PhD, a postdoctoral researcher in Krogan’s Lab – and in collaboration with Danielle Swaney at the Gladstone Institutes and Pedro Beltrao at the European Molecular Biology Laboratory’s European Biosciences Institute in in Cambridge, England – revealed that 49 kinases exhibited abnormal activity in infected cells. In particular, the researchers found that a well-studied kinase network known as the p38/MAPK pathway, which is known to trigger the production of inflammation-inducing cytokines, was significantly more active. This finding may help explain the so-called cytokine storms – a hyperactive immune response that damages organs – frequently associated with severe cases of COVID-19. The researchers also found that the CDK kinases, which control the cell cycle, were significantly less active during infection, which halted the resource-intensive process of cell division in order to funnel more resources toward virus production.

But perhaps most surprising was the international team’s finding that SARS-CoV-2 activated a kinase called CK2, which in turn appeared to stimulate the production of filopodia, tiny tentacle-like protuberances that extend out from the cell’s surface.

Using microscopic techniques, a group at the University of Freiburg in Germany led by Robert Grosse, Dr. Med., showed that SARS-CoV-2 and CK2 “colocalize” in infected cells, likely contributing to the formation of filopodia. With electron microscopy, Elizabeth R. Fischer and colleagues at Rocky Mountain Laboratories, operated by the National Institute of Allergy and Infectious Diseases, zoomed in to capture the first-ever images of the virus budding from these structures.

Though other viruses – including Ebola, Marburg and vaccinia – are known to give rise to filopodia and to use them as a kind of railway along which those viruses can travel to reach other cells, this is the first time that filopodia have been observed in association with any member of the coronavirus family. Though it remains to be confirmed, the scientists believe that SARS-CoV-2 may also use filopodia as an infective transport system.

After identifying the kinases that SARS-CoV-2 depends on for survival, the scientists compiled a list of existing drugs known to target many of these kinases. If these drugs could successfully interfere with kinase activity in infected cells, they might be able to stop the virus in its tracks.

The scientists tested 68 such compounds and found that those that interfered with the activity of the CK2, p38/MAPK and CDK pathways exhibited potent antiviral activity without being toxic to cells, suggesting that a combination “cocktail” of these drugs could prove to be an effective way to treat COVID-19.

“We are encouraged by our findings that drugs targeting differentially phosphorylated proteins inhibited SARS-CoV-2 infection in cell culture,” said QCRG member Kevan Shokat, PhD, professor of cellular and molecular pharmacology at UCSF and co-senior author of the study. “We expect to build upon this work by testing many other kinase inhibitors while concurrently conducting experiments with other technologies to identify underlying pathways and additional potential therapeutics that may intervene in COVID-19 effectively.”

In addition to UCSF, Freiburg, and Rocky Mountain Laboratories, the work also included researchers from the European Molecular Biology Laboratory’s European Biosciences Institute in Cambridge, England; Icahn School of Medicine at Mount Sinai in New York; and Institut Pasteur in Paris, France. Please refer to the study for a full list of authors, affiliations and funding sources.

source https://scienceblog.com/517129/covid-19-relies-on-cells-master-regulators-for-survival/

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