Thread by @__ice9

@illiteralworst [hydroxy]chloroquine - antiviral and anti-inflammatory, multiple successful human trials and extensive anecdotal/case reports, known mechanism, now politically controversial

favipiravir - antiviral, one human trial and earlier case reports, known mechanism, not approved in U.S.

@illiteralworst umifenovir - interferon inducer, 3 human trials including one for prevention, known mechanism, effects a bit weak, must use very early (best in advance)

lopinavir-ritonavir - antiviral, at least 3 human trials, weak performer, probably does not work unless in huge doses

@illiteralworst inhaled nebulized interferon - reports of successful human use, seemingly effective baseline in one trial but never properly compared, known mechanism, best used early

tocilizumab - one very successful trial, anti-IL6 anti-inflammatory, rescue for severe cases and critical/ARDS

@illiteralworst azithromycin - used in two trials with HCQ but never directly tested with sufficient power, extensive anecdotal support including a friend, anti-inflammatory, prevents secondary bacterial pneumonia, no proven antiviral effect

inhaled or IV-pulse steroids - anti-inflammatory

@illiteralworst ciclesonide - unusual inhaled steroid anti-inflammatory with antiviral effects against coronaviruses, known mechanism, several very good case studies in Japan plus anecdotal clinical support from Japan, already widely available

sarilumab - likely about the same as tocilizumab

@illiteralworst remdesivir - antiviral with known mechanism, still has not released any trial data but seems to be building a decent record of efficacy reports, IV-only, worse side effects than most, probably only good for severe early cases

convalescent plasma - likely helps but only early

@illiteralworst high dose vitamin C - increasingly widespread favorable anecdotal reports as part of supportive therapy, unlikely to have much direct effect against virus, likely to improve immune response

potassium - widespread reports of hypokalemia, which this fixes

@illiteralworst apart from that, here are a few widely-approved existing human drugs that have still not yet been tested in humans against coronaviruses, but work in vitro and in animal models:

- nitazoxanide
- niclosamide
- indomethacin
- itraconazole

@illiteralworst also nelfinavir - likely about the same as lopinavir-ritonavir, may be slightly more effective based on predictions from simulation but unclear, no human trial evidence to date

@illiteralworst Here are the putative mechanisms for the ones I just listed:

https://twitter.com/__ice9/status/1244096263873859585?s=19

@illiteralworst There are also a small number of OTC options with in vitro evidence, the most plausible and accessible currently being:
- isoquercetin
- concentrated echinacea extract
- concentrated elderberry extract (but only shown for other coronaviruses)
- scutellarin

@illiteralworst Many OTC formulations have bioavailability issues, and most have unacceptable systemic toxicity at their in vitro IC50s. For example, *avoid*:
- EGCG (green tea extract)
- glycyrrhizin (licorice extract)
- emetine (castor oil)
- lycorine (various flowers)
These are only a few.

@illiteralworst There is more circumstantial evidence for:
- lactoferrin (bioavailability likely to be limiting)
- high dose garlic extract (no direct testing)
- bromhexine (limited testing)

ARB anti-hypertensives also appear to have protective effects in a retrospective study, but that's all.

@illiteralworst As a general prophylactic measure, there is also some evidence from other viral respiratory tract infections that frequent mouthwash gargling may marginally reduce the risk and severity of such illnesses. Minor but no significant risks. Alcohol, H2O2, or 1% povidone iodine.

@illiteralworst It is probably worth noting that none of the OTC items listed above appear to be nearly as potent as the pharmacological ones. I am listing them mostly for completeness.

I also omitted many drugs with in vitro activity but major systemic toxicity at doses needed to hit IC50.

@illiteralworst See thread above for my views on the landscape of currently proposed and implemented treatments and preventative measures for COVID-19.