Why chloroquine should not be used for Covid-19 treatment

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London:  The antimalarial drug chloroquine widely rumoured to help prevent Covid-19 is not able to prevent infection of human lung cells with the novel coronavirus, say German researchers.

The current study, published in the journal Nature, revealed that chloroquine is, therefore, unlikely to prevent the spread of the virus in the lung and should not be used for the treatment of Covid-19.

“In this study, we show that the antiviral activity of chloroquine is cell type-specific and that chloroquine does not block the infection of lung cells,” said study researcher Stefan Pohlmann from German Primate Centre (DPZ) in Germany.

It is known that SARS-CoV-2 is able to use two different routes to enter cells.

First, after attaching to the cells, the virus can fuse directly with the plasma membrane and introduce its genetic material into the host cell. Second, it can enter the interior of the cells upon uptake via transport structures, called endosomes.

In both cases, the attachment of the virus to the cells and subsequent entry is mediated by the viral spike protein.

For this purpose, the spike protein must be activated either by the enzyme cathepsin L (in endosomes) or by the enzyme TMPRSS2 (on the cell surface).

Depending on the cell type, both enzymes or only one of them can be available for activation.

Since chloroquine inhibits the infection of monkey kidney cells with SARS-CoV-2, chloroquine has been tested in clinical trials as a possible candidate for the treatment of Covid-19.

However, how chloroquine inhibits the infection of monkey kidney cells was not clear.

The current study shows that chloroquine inhibits viral entry into these cells, most likely by blocking cathepsin L activity.

This raised the question of whether chloroquine also inhibits the infection of lung cells that are known to produce TMPRSS2 but only a small amount of cathepsin L.

The study shows that chloroquine does not prevent SARS-CoV-2 entry into human lung cells and the subsequent spread of the virus in these cells.

“This means that in future tests of potential Covid-19 drugs, care should be taken that relevant cell lines are used for the investigations in order not to waste unnecessary time and resources in our search for effective Covid-19 therapeutics,” Pohlmann added.

Recently, a study published in the journal Annals of Internal Medicine, revealed that the famous anti-malarial drug hydroxychloroquine (HCQ) was ineffective for Covid-19 patients with early and mild symptoms.

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