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@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 Seems to conflict somewhat with results reported here, which imply large doses.

biorxiv.org/content/10.110…

>we show that the addition of heparin (100 μg/mL) to Vero cells inhibits invasion by SARS-CoV-2 by 70%.

That is equivalent to 500mg heparin, huge overdose.
@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 Ah I see. Alternate variants have different EC50 (and Spike binding affinities):
news.rpi.edu/content/2020/0…

>RPI-27 yielded an EC50 value of approximately 83 nanomolar
>Heparin yielded an EC50 of 2.1 micromolar
>non-anticoagulant analog of heparin yielded an EC50 of 5.0 micromolar
@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 Press release from RPI:
news.rpi.edu/content/2020/0…

Original article:
sciencedirect.com/science/articl…

Very different results for different heparin variants.

This lab specializes in creating synthetic heparins.
@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 Viral replication assay paper:
nature.com/articles/s4142…

The extremely low _molar_ EC50 value is related to the very high molecular weight (~100,000g/mol) of the heparin variant tested.

Section (d) of image 4 below shows mass fractions: lower than normal heparin, but not much.
@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 However, these alternate variants are all indicated as non-anticoagulant forms of heparin, with low cytotoxicity.

Just keep in mind:

These are not standard enoxaparin or unfractionated heparin.

They are not on the market yet.

Ordinary heparin use will not block SARS-CoV-2.
@ishan_bhupendra @drakchaurasia @Thinkerks @NG20194 @DrSubhasree @Dharmen46587056 Also see this related study discussing Spike binding to cell surface heparan sulfate, may perhaps be involved to some extent in anchoring Spike:

biorxiv.org/content/10.110…

Notes on heparin vs. heparan sulfate:

sigmaaldrich.com/technical-docu…

ncbi.nlm.nih.gov/pmc/articles/P…
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ice9
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@monarchdiaries @halvorz @lewistlc @pathdoc3 @88549439 @csentropy @AndyBiotech @julienpotet @Crashcart @gstanchev @Hongma123 @YinPD @assur153 In early hospitalized cases.

By definition, endosomal entry inhibitors only protect against free virions, entering by endocytosis.

The mechanism is not relevant to cell-cell fusion, or to TMPRSS2-mediated fusion with a free virion at the cell membrane itself.
@monarchdiaries @halvorz @lewistlc @pathdoc3 @88549439 @csentropy @AndyBiotech @julienpotet @Crashcart @gstanchev @Hongma123 @YinPD @assur153 @macroliter @VirusWhisperer noticed reply on possible effects from variation in receptor expression on the rate of syncytial cell-cell fusion, in spite of structural support from the infected cell's cytoskeleton, and thought this thread might interest you.
@monarchdiaries @halvorz @lewistlc @pathdoc3 @88549439 @csentropy @AndyBiotech @julienpotet @Crashcart @gstanchev @Hongma123 @YinPD @assur153 @macroliter @VirusWhisperer Also see this paper on entry routes:

ncbi.nlm.nih.gov/pmc/articles/P…

This is a good overview of comparative CoV entry for SARS-CoV, MERS-CoV, and SARS-CoV-2.

This section discusses what I mentioned about fusion at the cell membrane directly if TMPRSS2 is available.
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@monarchdiaries I am increasingly wondering whether the Chinese HCQ trials can be trusted.

It is possible that the government needed to quickly propose some kind of near-term solution, and may have somehow inflated efficacy estimates.

The nebulized interferon results replicate well, at least.
@monarchdiaries It is reasonable to think an entry inhibitor might work better in the presence of an interferon inducer (or interferon), which I thought might explain the discrepancy in later results reported for HCQ alone (often RCTs) versus HCQ+AZM/IFN/etc. (often merely observational).
@monarchdiaries Some RCTs were also poorly designed in other respects, e.g. RECOVERY massively overdosing everyone and trying to treat severe cases with it.

I spent considerable time excoriating Horby over that. It is genuinely scandalous, regardless of whether HCQ helps milder cases or not.
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@__ice9
@poiThePoi It should still provide partial protection, particularly via vaccination since that seems to outperform natural infection in most cases, but it suggests the population vaccination rate may need to be very high.
@poiThePoi This is a problem, because the vaccines continue to be associated with rather unpleasant and, in rare cases, potentially dangerous adverse effects.
@poiThePoi They also all seem to need a booster dose about 3-4 weeks after the first one, which is likely to reduce compliance due to people simply forgetting or changing their mind about it.
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