Thread by @modrak_m

I've been helping my wife (who is a pharmacist at a local hospital) with literature review for possible drugs against #COVID19. Blindly tagging some people I believe might provide further comment (based on Twitter search) @julie_justo @EmilySpivak
@Dr_Mike_Stevens
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Disclaimer first: I am NOT a medical professional, and this is not medical advice. I'm sharing if someone wants a starting point or add other good stuff. Also, we don't really know anything, there is no truly reliable data, all the evidence is weak and/or indirect. 2/N

Gratitude second: thanks to all the authors who put their work online quickly. Those are difficult times and I greatly admire everybody's hard work. So, let's start with #chloroquine and #HydroxyChloroquine which has seen some enthusiasm recently. 3/N

Bad news: Touret & Lamballerie warn that #chloroquine used to be promising in cell lines for multiple viral diseases but always failed to deliver in vivo, sometimes even making things worse. Utmost caution necessary. sciencedirect.com/science/articl… 4/N

Now the positive case: Colson et al. summarise multiple studies showing efficacy of chloroquine on various longer-known coronaviruses, mostly in monkey cell lines but also in mice and share their personal experience with the drug and dosing sciencedirect.com/science/articl…
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Yao et al. apply the actual SARS-CoV-2 (unlike some others who use artificial constructs including some SARS-CoV-2 proteins) to Vero (monkey cells), show efficacy and model pharmacokinetics to asses optimal dose. academic.oup.com/cid/advance-ar… 6/N

Wang et al. measure both efficacy and (importantly) cell toxicity of several compounds. Real viral particles, monkey cells. Remdesivir and chloroquine show the biggest gap between concentrations that inhibit the virus and those that are toxic nature.com/articles/s4142… 7/N

Gao et al., report that preliminary analysis of 100 patients involved in clinical tests with chloroquine look good. No real data/methods shown, also the early unblinding is potentially worrying, hard to judge how to take this. jstage.jst.go.jp/article/bst/ad… 8/N

The above evidence led the Chinese authorities to include chloroquine in its official guidelines which provide indication, contra-indication and dosage (in Chinese, the screenshot is from Google Translate): rs.yiigle.com/yufabiao/11823… 9/N

I also found some reports that South Korea is using chloroquine as well, but I could not verify from a good source koreabiomed.com/news/articleVi… 9/N

Generally, there are reasons to believe that drugs that worked on SARS-CoV or other coronaviruses could also work on SARS-CoV-2. Li&Clercq summarise some of the options, mostly based on Wang et al. (shown above). Remdesivir comes out as promising. nature.com/articles/d4157… 10/N

There are also reasons to believe SARS-CoV drugs to not help, e.g. Morse et al. review, which however still suggests Remdesivir as potentially useful along with some as yet clinically unapproved compounds. They throw some shade on Ribavirin (RBV). onlinelibrary.wiley.com/doi/pdf/10.100… 11/N

Hoffman et al, show efficacy of camostat mesylate in preventing viral activity within cells by blocking a protease TMPRSS2 that they deem vital for SARS-CoV-2 (human lung cells, artificial viral particles). Camostat mesylate is approved in Japan. sciencedirect.com/science/articl…
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Hoffman et al. also discuss potential source of differences and similarities between SARS-CoV and SARS-CoV-2, but the discussion is way above what I can understand - check the paper out. They also admit that TMPRSS2 might be (partially) substituted by Cathepsin-L 13/N

Preprint by Zhang et al. attempts to attack the same step in the viral lifecycle as Hoffman et al., but they show activity of Teicoplanin against Cathepsin-L, claimin this is the vital protease. The effects are not staggering, human cancer cell-lines. biorxiv.org/content/10.110… 14/N

Finally, Li, Wang & Wang have a neat review of approved drugs that showed some effects against influenza and coronaviruses (this came out a year ago, so ignores SARS-CoV-2) onlinelibrary.wiley.com/doi/pdf/10.100… 15/N

Once again, thanks for everybody's hard work and hope somebody finds this useful. If you have stuff to add, please do!