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PeterKolchinsky's profile
Peter Kolchinsky
Peter Kolchinsky
Peter Kolchinsky
@PeterKolchinsky

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Peter Kolchinsky

@PeterKolchinsky

Managing Partner, RA Capital Management. We build & invest in biotech companies. Virologist. Author, The Great American Drug Deal. http://amzn.com/1733058915/ 

Boston, MA
racap.com
Joined May 2019

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    Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

    While not technically alive, there's an evil genius to viruses that never ceases to amaze me. It's one reason I became a virologist. A recent Nature paper reveal a remarkable trick SARS-Cov-2 learned that makes it nastier than the first SARS. Both viruses…

    6:37 PM - 5 Apr 2020
    • 21,643 Retweets
    • 48,524 Likes
    • Darren Deuser mel 🍑 Mary Javier Banchs Matt Jepson Radhika0611 Happy heathen Fly on the wall Jim McCasland
    1,067 replies 21,643 retweets 48,524 likes
      1. New conversation
      2. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …attach via their external spike protein to a protein on our cells called ACE2. Think of it as a particular doorknob that the virus knows how to turn. Every virus has a particular type of doorknob that it attaches to and turns so it can enter (infect) a cell.

        40 replies 544 retweets 3,833 likes
        Show this thread
      3. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        For example, HIV has to turn two doorknobs: CD4 and typically CCR5. MERS attached to one called DPP4. All our cells are covered in all kinds of proteins that make them distinctive from one another. Those proteins aren’t there to let in viruses. They have all kinds of functions…

        12 replies 436 retweets 3,270 likes
        Show this thread
      4. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …such as regulating blood pressure, our immune response, sugar levels in our blood, etc. But viruses have evolved to grab onto one or more proteins to gain entry into cells, where they hijack the cell’s machinery to make more viruses. (Viruses can't replicate on their own...

        9 replies 427 retweets 3,252 likes
        Show this thread
      5. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        ...& hence, are not quite alive). So what viruses see are a bunch of houses w/ varying doorknobs & they try to spread through the neighborhood (our bodies) looking for houses (cells) covered in the doorknobs that they know how to turn. HIV enters T cells b/c T cells are...

        10 replies 379 retweets 3,013 likes
        Show this thread
      6. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …covered in CD4 & CCR5 doorknobs that HIV knows how to turn. That makes HIV the kind of virus that destroys our immune system. Well, the ACE2 doorknob that SARS-1 & SARS-2 use is present on a variety of cells, including those in our lungs & throat. SARS-1 would enter a person…

        14 replies 373 retweets 2,866 likes
        Show this thread
      7. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …via a droplet in the air (from cough) & quickly start infecting lung cells, causing severe damage person could really feel (i.e. become symptomatic). In other words, SARS-1 quickly made its presence known. In some patients, SARS-1 would go into the upper airways to replicate...

        5 replies 380 retweets 2,797 likes
        Show this thread
      8. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        ...from where it could spread to others with a cough (or just breathing). But b/c SARS-1 patients got very sick from all the virus replicating in their lungs, they were quarantined before others got close enough to get sneezed or coughed on.

        7 replies 388 retweets 2,869 likes
        Show this thread
      9. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        SARS-2, on the other hand, takes up residence in the throat cells first, which doesn’t cause significant symptoms. The person can remain asymptomatic or might not think they have anything worse than a cold. And from that person’s throat…

        44 replies 689 retweets 3,572 likes
        Show this thread
      10. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …it can readily spread to others. Over the course of a week, in some patients, it will move into the lung neighborhood and replicate just as SARS-1 would, causing severe symptoms, by which point the person is quarantined, but no matter since it had successfully spread.

        9 replies 481 retweets 3,052 likes
        Show this thread
      11. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        So SARS-1 was a comparatively dumb virus. It went straight for the lungs, announced itself before it could spread to others, and so got social distanced into extinction. But SAR-2, the one plaguing us now, is stealthier, spreading first before revealing itself (and causing harm).

        38 replies 1,277 retweets 5,195 likes
        Show this thread
      12. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        What’s the take-away for all of us? It’s that beating this virus means social distancing & wearing masks even if we think we aren’t infected. Because we might be. The virus might be replicating in our throats without us knowing (that’s its evil plan!), so put up a roadblock.

        50 replies 2,057 retweets 7,327 likes
        Show this thread
      13. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        These insights come to us thanks to the hard work of researchers in Germany who very carefully studied the replication patterns of SARS-CoV-2 in a small number of patients, measuring everything they could daily over the course of their infections. https://www.nature.com/articles/s41586-020-2196-x …

        22 replies 1,503 retweets 7,093 likes
        Show this thread
      14. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Another reassuring insight is that, as these patients’ immune systems revved up and produced antibodies, they stopped producing viable viruses. The researchers could still detect bits of the virus, but they couldn’t find evidence that, among those bits, there was any virus…

        13 replies 467 retweets 3,417 likes
        Show this thread
      15. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …that could actually infect cells. This isn’t a surprising result. It confirms what we already know about how we have survived viruses like this since humans first evolved. Our immune systems fight them off with antibodies. So when we have vaccines that…

        10 replies 371 retweets 3,028 likes
        Show this thread
      16. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        …prompt our immune system to produce high levels of such “neutralizing” antibodies that can inactive SARS-2, we’ll have a head start on the virus. Should any virus enter our bodies, those antibodies will help shut it down before it causes harm & keep it from spreading to others.

        20 replies 356 retweets 3,019 likes
        Show this thread
      17. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Some will say "what about antibody-directed enhancement". That's a known risk that can be detected in early animal & human studies. With all the vaccine programs out there, we'll have a good one (or several) that protects us from this pandemic and from future waves of SARS-Cov-2.

        41 replies 309 retweets 2,665 likes
        Show this thread
      18. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Some have asked, why would SARS1 and 2 infect throat & lung cells differently if they both use ACE2. Great question. There’s a lot more to viruses than which doorknobs they turn.

        14 replies 277 retweets 2,430 likes
        Show this thread
      19. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Besides spike protein, coronaviruses have many other parts that engage with our machinery. Let’s say SARS2 climbs stairs better & throat cells are a duplex (has stairs). So SARS1 gets tripped up in throat cells & prefers single-story lung cells.

        22 replies 258 retweets 2,271 likes
        Show this thread
      20. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Peter Kolchinsky Retweeted Peter Kolchinsky

        Also, some have questions about whether virus mutates too fast for a vaccine. Short answer, no. We’ll have a vaccine. Here’s detailed explanation. https://twitter.com/peterkolchinsky/status/1245121993919344640?s=21 …https://twitter.com/PeterKolchinsky/status/1245121993919344640 …

        Peter Kolchinsky added,

        Peter Kolchinsky @PeterKolchinsky
        Worried we might not get an effective #COVID19 vaccine b/c virus is mutating too fast? I’m a virologist & explain in @CityJournal why way coronaviruses replicate stacks odds of success well in our favor. Hint: it’s a cactus & not just b/c of its spikes. https://www.city-journal.org/coronavirus-vaccine …
        26 replies 685 retweets 3,354 likes
        Show this thread
      21. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        Peter Kolchinsky Retweeted Peter Kolchinsky

        And for those wondering how America’s insurance system is impacting this pandemic, I’ve written on that. Answer - not good. https://twitter.com/peterkolchinsky/status/1244976353595871232?s=21 …https://twitter.com/PeterKolchinsky/status/1244976353595871232 …

        Peter Kolchinsky added,

        Peter Kolchinsky @PeterKolchinsky
        COVID-19 is a pathogen but it’s also a diagnostic test being run on America’s health insurance system. The results are coming in and they aren’t good. We need immediate, emergency #insurancereform. For example, covid will give millions of healthy people a taste of...
        Show this thread
        22 replies 572 retweets 2,856 likes
        Show this thread
      22. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        And finally, if you like complex stuff made simple, have time for reading, & wonder what America can do to fix its healthcare affordability crisis, check out my new book. It’s like the Freakonomics of Drug Pricing. Won’t think of EpiPen & DTC the same.http://www.thegreatamericandrugdeal.com 

        29 replies 471 retweets 3,208 likes
        Show this thread
      23. Peter Kolchinsky‏ @PeterKolchinsky 5 Apr 2020

        And coincidentally, for this book, I researched and wrote about the most widely prescribed generic drug in America called lisinopril... it inhibits ACE1 (related but not same as ACE2) to control blood pressure. It’s just one story among many.

        165 replies 219 retweets 2,219 likes
        Show this thread
      24. Peter Kolchinsky‏ @PeterKolchinsky 3 May 2020

        In retrospect, the best thing about this thread is that it made some kids want to become scientists. Cool- we’ll need them. There’s still so much left to discover.

        8 replies 4 retweets 135 likes
        Show this thread
      25. End of conversation

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