This is a great piece from @rkhamsi about a topic that people often don't think about: it's REALLY important to consider the types of cells being used for in vitro experiments, especially those concerning #SARSCoV2 #COVID19 #coronavirus drug efficacy. https://www.wired.com/story/scientists-may-be-using-the-wrong-cells-to-study-covid-19/

VeroE6 cells are often used to culture viruses because they are convenient. They lack type 1 interferons (IFNs), which are antiviral proteins that can inhibit viral replication. They also grow continuously, unlike normal mammalian cells which eventually senesce (stop dividing).

They are aneuploid (they have an abnormal number of chromosomes). This is common in continuous cell lines since they undergo transformation to become continuous.

For VeroE6s, there is a large deletion on chromosome 12 that took out all the IFN genes, as well as genes controlling the cell cycle called cyclin dependent kinase inhibitors. This explains how they both are great for growing viruses, as well as continuously dividing.

In addition to being good for growing viruses because they have no IFNs themselves, they still have interferon receptors (the external protein IFN binds to and signals through), so you can add IFNs to study the response to IFN in Veros even though they don't actually make IFNs.

Also, this has nothing to do with their utility in doing in vitro experiments, but Wikipedia informs me that "Vero" means truth in Esperanto (lol)
https://en.wikipedia.org/wiki/Vero_cell 

While VeroE6's are great for growing up lots of virus to make lab stocks, and fine for looking at the mechanics of viral replication and IFN signaling, they are not so good for other things. Like, say, screening drugs that are supposed to work in people.

Veros are from the kidney of an African green monkey. So they are not human and they are not from the lung. They are transformed and have a huge genomic deletion. They are fundamentally different from a cell that #SARSCoV2 would infect in the real world.

So what? Well, a lot of the early in vitro studies showing that chloroquine/hydroxychloroquine might be an effective antiviral were done in Vero cells. Recently Stefan Pohlmann and colleagues showed that chloroquine was not effective in human lung cells. https://www.nature.com/articles/s41586-020-2575-3

Vero cells don't express TMPRSS2, but do express cathepsin L. These are proteins that can both enable #SARSCoV2 entry. CQ/HCQ blocks cathepsin L, but not TMPRSS2. Human lung cells, which do have TMPRSS2, are still susceptible to infection because CQ has no effect on that pathway.

Now I know this because I'm a virologist and I know all about Vero cells. But as both @profvrr and @paimadhu point out, when non-virologists start working on #COVID19 treatments using only Vero cells because they're convenient, the results can be misleading.

I regularly get HCQ believers in my replies triumphantly tweeting links to papers featuring in vitro studies using Vero cells that supposedly PROVE WITHOUT A DOUBT that it is effective.

Nah. I don't care how you frame it: these studies are inherently unable to address that.

We should not rush to start treating #COVID19 patients with drugs that show effects in Vero cells alone. They are nothing like cells in the human lung. Even human lung cell lines are inadequate to recapitulate the complex structure and biology of differentiated airway tissue.

This doesn't mean that something that shows promise in Vero cells isn't worth doing more studies on. But cool results in Veros should lead to doing additional studies in more relevant experimental models (human lung cells, primary airway cultures, animal models).

We should NOT start talking about miracle drugs and clinicians should not just start using things found in Veros for treating patients off-label. Look at how much time and resources and lives were wasted on HCQ (not to mention my patience with the HCQ zealots in my replies).

As @rkhamsi says perfectly, "The cells that scientists select are tiny, but their repercussions are anything but small."