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Antiviral compound blocks SARS-CoV-2 from entering cells

medicine.wustl.edu

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Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#3

We already have a treatment that works fine. Get some ivermectin and chill.

> We already have a treatment that works fine. Get some ivermectin and chill.

This isn’t a helpful comment. Please read the hacker news guidelines

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#4
I wonder if they actually used human lung cells for this test; the article doesn’t seem to specify. Past tests have used Vero cells, which are apparently the norm for virology research, but aren’t a good analogue for human cells for Covid infection. This seems to be why some compounds worked well in a Petri dish, but didn’t work in actual humans.

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#5
I'm starting to get pretty optimistic. There seem to be a bunch of antivirals with very different mechanisms of action - this one blocks entry of the virus to cells, Molnupiravir fucks up accurate replication of the virus (nucleoside analog), others are protease inhibitors, which are very effective against HIV.

There's a caveat, most treatments that look promising don't pan out, but there are a lot in the pipeline and it seems likely that some will. What I think will happen is a cocktail of antivirals, and together these will significantly reduce the mortality. We need that, because it looks like the virus will probably be circulating endemically. The other great thing about a cocktail (as opposed to a single antiviral) is that the virus developing resistance is both less likely and less of a problem if it does happen.

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#6

I'm starting to get pretty optimistic. There seem to be a bunch of antivirals with very different mechanisms of action - this one blocks entry of the virus to cells, Molnupiravir fucks up accurate replication of the virus (nucleoside analog), others are protease inhibitors, which are very effective against HIV. There's a caveat, most treatments that look promising don't pan out, but there are a lot in the pipeline an…

mRNA vaccines look extremely promising too. It’s entirely possible that some classes of cancer will be effectively eliminated in our lifetime because of it, along with HIV and/or Malaria. The latter would probably be the biggest reduction in human death and misery since the invention of the Polio vaccine

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#7

I wonder if they actually used human lung cells for this test; the article doesn’t seem to specify. Past tests have used Vero cells, which are apparently the norm for virology research, but aren’t a good analogue for human cells for Covid infection. This seems to be why some compounds worked well in a Petri dish, but didn’t work in actual humans.

Here's the actual paper: https://www.pnas.org/content/118/43/e2108728118

There's a lot of detailed discussion about different types of cells. Vero cells don't have TMPRSS2, but Calu-3 (human lung epithelial) cells do. To dramatically oversimplify, this compound works on the latter type but not the former.

They also did a little safety testing in a mouse model. This is early stage, as you point out there are a lot of things that work well in the lab and not so much in real humans, but still I find it promising.

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#8

We already have a treatment that works fine. Get some ivermectin and chill.

> We already have a treatment that works fine. Get some ivermectin and chill. This isn’t a helpful comment. Please read the hacker news guidelines

It is helpful. Ivermectin works so well Pfizer is copying it.

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#9

I wonder if they actually used human lung cells for this test; the article doesn’t seem to specify. Past tests have used Vero cells, which are apparently the norm for virology research, but aren’t a good analogue for human cells for Covid infection. This seems to be why some compounds worked well in a Petri dish, but didn’t work in actual humans.

Here's the actual paper: https://www.pnas.org/content/118/43/e2108728118 There's a lot of detailed discussion about different types of cells. Vero cells don't have TMPRSS2, but Calu-3 (human lung epithelial) cells do. To dramatically oversimplify, this compound works on the latter type but not the former. They also did a little safety testing in a mouse model. This is early stage, as you point out there are a lot of…

I’m not the best reader of scientific papers, but it looks like they used human lung cells and Vero cells. I’m not qualified to speak to the rest of the experimental design, but it looks like they’ve at least avoided that old mistake.

> We analyzed pseudotype entry driven by the spike protein of SARS-CoV-2 (SARS-2-S) or the glycoprotein of vesicular stomatitis virus (VSV-G) into the TMPRSS2-positive human lung cell line Calu-3 (7, 29). VSV-G was used as a control, as it does not depend on TMPRSS2 for host cell entry. Besides Calu-3 cells, we further used Vero cells (African green monkey, kidney) as a control, as these cells do not express TMPRSS2, and therefore any reduction in SARS-2-Sdriven entry would be related to either unspecific side effects or cytotoxicity.

Re: Antiviral compound blocks SARS-CoV-2 from entering cells

#10

Earlier quoted context omitted.

> We already have a treatment that works fine. Get some ivermectin and chill. This isn’t a helpful comment. Please read the hacker news guidelines

It is helpful. Ivermectin works so well Pfizer is copying it.

https://apnews.com/article/fact-checking-067310377629
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