Chloroquine does not inhibit SARS-CoV-2: study

German researchers have shown that the malaria drug chloroquine, which has been demonstrated to inhibit SARS-CoV-2 infection of African green monkey kidney cells, is not able to prevent infection of human lung cells. Their findings, published in the journal Nature, indicate that chloroquine is thus unlikely to prevent the spread of the virus in the lung and should not be used for the treatment of COVID-19.

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, the malaria drug has been tested in clinical trials as a possible candidate for the treatment of COVID-19. Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research, together with colleagues at the Charité – Berlin University of Medicine and the University of Bonn, found that the drug inhibits viral entry into kidney 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 team’s study shows that chloroquine does not prevent SARS-CoV-2 entry into human lung cells and subsequent spread of the virus in these cells. As noted by Stefan Pöhlmann, Head of the Infection Biology Unit at DPZ, “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.

“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.

“COVID-19 is primarily caused by the infection of lung cells; for this reason, these cells should be given priority in efficacy tests.”

Image caption: Dr Markus Hoffmann examines a cell culture under the microscope. Image credit: Nadine Krüger.

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