Researchers in Germany have discovered that malaria drug chloroquine cannot prevent infection of human lung cells with the novel coronavirus. Only recently, the drug was proved to be effective in inhibiting the SARS-CoV-2 infection African green monkey kidney cells.
The Infection Biology Unit of the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen, together with colleagues at the Charité in Berlin, was able to show that chloroquine is unlikely to prevent the spread of the virus in the human lung and should not be used for the treatment of COVID-19. Their study has been published in Nature.
SARS-CoV-2 enters cells through two different routes: First, directly via the plasma membrane, and the second, through the interior of the cells upon uptake via transport structures, called endosomes.
The viral spike protein plays the most important role in both cases. 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.
Chloroquine is a drug that is used to treat malaria. 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 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 subsequent spread of the virus in these cells.
“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,” says Stefan Pöhlmann, head of the Infection Biology Unit at DPZ, adding: “COVID-19 is primarily caused by the infection of lung cells, for this reason these cells should be given priority in efficacy tests.”
