TWiV explains why hydroxychloroquine failed in humans despite showing antiviral effects in cells, and reviews the published data on the Pfizer/BioNTech mRNA vaccine.
Hosts: Vincent Racaniello, Rich Condit, Kathy Spindler, and Brianne Barker
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Download TWiV 715 (66 MB .mp3, 110 min)
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Links for this episode
- TMPRSS2 is why hydroxychloroquine failed (PLoS Path) 3:58
- Safety and efficacy of BNT162b2 mRNA vaccine (NEJM) 39:48
- Letters read on TWiV 715 1:05:10
- Timestamps by Jolene. Thanks!
Weekly Picks 1:35:57
Brianne – How the Body Reacts to Viruses
Rich – How do wombats poop cubes?
Kathy – The Verse by the Side of the Road
Vincent – Janet Iwasa’s SARS-CoV-2 entry animation
Intro music is by Ronald Jenkees
Send your virology questions and comments to twiv@microbe.tv
youtube poster image is wrong: #715 iso #717
This paper makes a nice complement to the HCQ one discussed today. Now that people are thinking more about the two entry pathways, I suppose we’ll see a lot of previously-rejected antivirals being revisited, now in combination with Camostat.
“Camostat mesylate may therefore be used in combination with, for example, corticosteroids and Remdesivir to reduce cell entry, replication and inflammation. The antiviral potential of camostat mesylate has attracted significant attention, and multiple clinical trials are either actively recruiting or planned. As of September 2020, 12 clinical trials have been registered to test camostat mesylate in up to 3000 patients and some of the trials have registered more than one cohort. Eight of the trials are randomized, double or quadruple, blinded studies with clinical endpoints including viral load, hospitalization days and mortality. Eight trials are testing camostat mesylate as a monotherapy on hospitalized patients, seven trials are on outpatient cohorts and three trials are as add‐on therapies in combination with other drugs.”
https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13533
Interestingly, in this paper from March 2020, though they were still assuming endocytosis alone at the time, the authors still anticipated the value of camostat mesylate.
So, now the world is nearly a year behind in following up one of the best leads for possible treatment. 🙁
“Indeed, the clinically proven serine protease inhibitor camostat mesylate, which is active against TMPRSS2 (Kawase et al., 2012), partially blocked SARS-2-S-driven entry into Caco-2 (Figure S3 B) and Vero-TMPRSS2 cells (Figure 4 A). Full inhibition was attained when camostat mesylate and E-64d, an inhibitor of CatB/L, were added (Figure 4A; Figure S3B), indicating that SARS-2-S can use both CatB/L as well as TMPRSS2 for priming in these cell lines. ”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102627/
Can you double-check the link to: ‘Janet Iwasa’s SARS-CoV-2 entry animation’? It’s not leading anywhere.
2:00 “We may get another freeze yet”. LOL. The understatement of the year, spoken from Texas.