Here's Why Hydroxychloroquine Doesn't Block The Coronavirus
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A paper came out in Nature that further underscores earlier studies that show that neither the malaria drug hydroxychloroquine nor chloroquine prevents SARS-CoV-2 – the virus that causes COVID-19 – from replicating in lung cells.

The new study was carried out by scientists in Germany who tested HCQ on a collection of different cell types to figure out why this drug doesn’t prevent the virus from infecting humans.

Their findings clearly show that that HQC can block the coronavirus from infecting kidney cells from the African green monkey. But it does not inhibit the virus in human lung cells – the primary site of infection for the SARS-CoV-2 virus.

In order for the virus to enter a cell, it can do so by two mechanisms - one, when the SARS-CoV-2 spike protein attaches to the ACE2 receptor and inserts its genetic material into the cell. In the second mechanism, the virus is absorbed into some special compartments in cells called endosomes.

Depending on the cell type, some, like kidney cells, need an enzyme called cathepsin L for the virus to successfully infect them. In lung cells, however, an enzyme called TMPRSS2 (on the cell surface) is necessary. Cathepsin L requires an acidic environment to function and allow the virus to infect the cell, while TMPRSS2 does not.

In the green monkey kidney cells, both hydroxychloroquine and chloroquine decrease the acidity, which then disables the cathepsin L enzyme, blocking the virus from infecting the monkey cells. In human lung cells, which have very low levels of cathepsin L enzyme, the virus uses the enzyme TMPRSS2 to enter the cell. But because that enzyme is not controlled by acidity, neither HCQ and CQ can block the SARS-CoV-2 from infecting the lungs or stop the virus from replicating.

Why it matters:
This matters for several reasons. One, much time and money has been spent studying a drug that many scientists said from the very beginning was not going to be effective in killing the virus. The second reason is that the studies that have reported antiviral activity for hydroxychloroquine were not in epithelial lung cells. Thus, their results are not relevant to properly studying SARS-CoV-2 infections in humans.

What’s next?
As scientists proceed with investigating new drugs as well as trying to repurpose old ones, like hydroxychloroquine, it is critical that researchers take the time to think about their study design.

Source: https://www.nature.com/articles/s41586-020-2575-3
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