Please, answer @s_r_constantin's question. I am most interested on that.
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Replying to @limits_stop @s_r_constantin
Yes. I have collections of papers for in vitro results against SARS-CoV-2, as well as SARS-CoV, MERS-CoV, some of the weaker human CoVs, and animal CoVs. The high throughput screening studies are the most useful, short of dedicated compound-specific investigations.
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Replying to @__ice9 @limits_stop
me too, but most of these are repurposed drugs for other uses. i'm just asking about your process. (I could of course make my own spreadsheet & try to convert the therapeutic dose in humans to an in-vitro equivalent? but too lazy rn).
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Replying to @s_r_constantin @limits_stop
Yes, I did a thread on new candidates as well a little while ago, but they have more potential safety risks.... Also relative concentrations for related CoVs tend to be off somewhat relative to SARS-CoV-2, so I try to get direct confirmation. SARS-CoV usually +/-50% though.
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For dose estimation from in vitro IC50/IC90, an *optimistic* guess starts at: g/mol * IC50(/90) mol/L * 50-70L / bioavail This usually undershoots actual pharmacokinetics a bit. Specific papers on pharmacokinetics (esp. tissue specific) better if can be located.
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Lung-specific tissue concentrations can be more useful than plasma, especially since antivirals generally make the most sense when used early. If patient already has widespread multiple organ infection and inflammation, then antivirals are secondary anyway.
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The most promising already-approved antiviral candidates I have seen with no human SARS-CoV-2 trial data yet are probably: - nelfinavir - nitazoxanide - niclosamide - nebulized niclosamide - ciclesonide (only case studies so far) - indomethacin - pyronaridine - itraconazole
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Replying to @__ice9 @limits_stop
that's got large overlap with my list, thanks!
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...?
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sorry, was busy. Indomethacin, niclosemide, ciclesonide, HTCC polymer, azithromycin, maybe amodiaquine if we're living dangerously, and INF-I.
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Replying to @s_r_constantin @limits_stop
ice9 Retweeted ice9
Check out doxycycline. Much less QTc prolongation risk than AZM and already validated against SARS-CoV-2 in cell culture, not just speculated--https://twitter.com/__ice9/status/1250037295530545154?s=19 …
ice9 added,
ice9 @__ice9Recent pre-print claims replication inhibition for doxycycline vs. SARS-CoV-2 (EC50=5.6µM). Caveat: Raoult not an author, but same affiliated clinic (IHU); grain of salt etc. Mid-high dose. Back of envelope: ~177mg @ 70% bioavail. Paper suggests 200mg (may be a bit low). https://twitter.com/alpha3xx/status/1250031331007922177 … pic.twitter.com/H2db4JMytHShow this thread1 reply 2 retweets 10 likes -
Mefloquine likely works from my estimates, but it's more toxic than chloroquine (similar mechanism), so I didn't include it. My impression is amodiaquine is similar, but not sure which one is less toxic (?). Conversely, pyronaridine (also related) appears less toxic than CQ.
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