Thread by @jschoggins

Never thought we’d contribute to clinical trial for COVID-19, but here we are. With @HeshamS70605263 team, we found FDA-approved drugs that curb SARS-CoV-2 in cells. Clinical trial pending approval. Study in Chemrxiv. Details in thread. 1/10
doi.org/10.26434/chemr… via @figshare

Here’s how it happened. @HeshamS70605263 team used computers (‘molecular docking’) to find FDA-approved drugs that might target a SARS-CoV-2 protein. Like a key fitting into a lock. If the drug fit, it might hinder the virus. 2/10

They combed through 2000 FDA-approved drugs and whittled the list down to ~24 drugs that looked like promising candidates for repurposing as antivirals for SARS-CoV-2/COVID-19. 3/10

We then jumped in and tested these 24 drugs for antiviral activity against the live SARS-CoV-2 virus in cell culture. Sure enough...some had antiviral activity! Hits that seem particularly attractive include Atovaquone, Mebendazole, and Ouabain. 4/10

This is now being passed on to the medical folks to get a clinical trial approved to test whether one of these drugs might be helpful in COVID-19 patients. Hard to predict outcome, but fingers crossed! If it doesn’t work, glad we at least tried. 5/10

Huge thanks and credit to the scientists who contributed: Ayman Farag, Ping Wang, Mahmoud Ahmed working with Hesham Sadek @HeshamS70605263 and our crack team of virologists-turned-drug screeners: @_iboys @jennuinelyjenn5 @MaikkeO @Wenchun_Fan @mattbmcdoug 6/10

Some details for the science wonks: molecular docking targeted central and terminal site of SARS-CoV-2 Mpro. Independent analysis focused on drugs with predicted covalent binding to active site. 3 of 7 ‘covalent binders’ were antiviral without being toxic! 7/10

For viral assay we chose Taqman RT-PCR to quantify SARS-CoV-2 viral RNA, rather than cell death readout, hoping this would be more direct/relevant. Initial screen was 6pt curve over 6log10 dilution. Validation was 10pt curve for IC50 determination. All biological duplicates. 8/10

Though lab open during shutdown, had to social distance and have only few people in BSL3, so set up pipeline:
Cells: @mattbmcdoug
Drugs: @_iboys
BSL3 infection: @_iboys and me
RNA harvest: @MaikkeO @Wenchun_Fan
Toxicity counterscreen: @MaikkeO
RT-PCR: @jennuinelyjenn5 9/10

Immensely proud of everyone’s commitment and effort! Up next....structure-function follow up of these hits...and...

...an entirely separate drug screening collaboration using different docking strategy...stay tuned!! 10/10