More than 600,000 people worldwide have been victims of lung disease COVID-19 so far, which is caused by SARS coronavirus-2 (SARS-CoV-2) To get effective therapy for COVID-19 as quickly as possible, the drugs being used to treat other diseases are being reused for COVID-19 treatment.
The Infection Biology Unit of the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen, together with colleagues from Charité in Berlin, were able to demonstrate that the anti-malaria drug, chloroquine, has been shown to inhibit SARS-CoV -2 infection of African green monkey kidney cells, is not able to prevent infection of human lung cells with the new coronavirus. Therefore, chloroquine is unlikely to prevent the spread of the virus in the lung and should not be used for the treatment of COVID-19.
SARS-CoV-2 is known to use two different routes to enter cells. First, after binding to cells, the virus can directly fuse with the plasma membrane and introduce its genetic material into the host cell. Second, it can enter cells inside cells after uptake through transport structures called endosomes. In both cases, virus binding to cells and subsequent entry is mediated by the viral peak protein. For this purpose, the spike protein must be activated by the cathepsin L enzyme (in endosomes) or by the TMPRSS2 enzyme (on the cell surface). Depending on the cell type, both enzymes or only one of them may be available for activation.
Dr. Markus Hoffmann examines a cell culture under a microscope. Credit: Nadine Krüger
Chloroquine is a medicine that is used to treat malaria. Since chloroquine inhibits infection of monkey kidney cells with SARS-CoV-2, chloroquine has been tested in clinical trials as a potential candidate for the treatment of COVID-19. However, how chloroquine inhibits monkey kidney cell infection was unclear. 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 infection of lung cells known to produce TMPRSS2 but only a small amount of cathepsin L.
The study shows that chloroquine does not prevent the entry of SARS-CoV-2 into human lung cells and the 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 infection of lung cells. This means that in future tests of potential COVID-19 drugs, care must be taken that research-relevant cell lines are used so as not to waste unnecessary time and resources in our search for effective COVID-19 therapies, “says Stefan Pöhlmann , head of the Infection Biology Unit at DPZ, added: “COVID-19 is mainly caused by infection of lung cells, for this reason these cells should be given priority in efficacy tests.”
Reference: “Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2” by Markus Hoffmann, Kirstin Mösbauer, Heike Hofmann-Winkler, Artur Kaul, Hannah Kleine-Weber, Nadine Krüger, Nils C. Gassen, Marcel A. Müller, Christian Drosten and Stefan Pöhlmann, July 22, 2020, Nature.
DOI: 10.1038 / s41586-020-2575-3
The study was carried out in cooperation with Charité in Berlin and the University of Bonn.
