German researchers identify existing drug with potential to treat coronavirus Covid-19

As the daily deaths from coronavirus decrease worldwide, a team of scientists from German Primate Centre, Charité, the University of Veterinary Medicine Hannover Foundation, the BG-Unfallklinik Murnau, the LMU Munich, the Robert Koch Institute, and the German Center for Infection Research, just made a startling discovery about potential drug that could treat coronavirus Covid-19. They  found that an existing drug camostat mesilate might protect against COVID-19.

The researchers made the stunning discovery while trying to find out how the new coronavirus SARS-CoV-2 enters host cells and how the process could be blocked. In a related development, Taiwanese genome researchers also made a breakthrough with the development of a rapid 15-minute COVID-19 diagnostic testing for coronavirus detection and screening.

Led by infection biologists from these five German research institutions, the researchers identified a cellular protein (protease TMPRSS2) that is important for the entry of SARS-CoV-2 into lung cells. Their study provides evidence that host cell entry of SARS-CoV-2 depends on the SARS242 CoV receptor ACE2 and can be blocked by a clinically-proven inhibitor of the cellular serine protease TMPRSS2, which is employed by SARS-CoV-2 for S protein priming.

According the researchers, viruses must enter cells of the human body to cause disease. For this, they attach to suitable cells and inject their genetic information into these cells. Infection biologists from the German Primate Center – Leibniz Institute for Primate Research in Göttingen, together with colleagues at Charité – Universitätsmedizin Berlin, have investigated how the novel coronavirus SARS-CoV-2 penetrates cells. They have identified a cellular enzyme that is essential for viral entry into lung cells: the protease TMPRSS2. A clinically proven drug known to be active against TMPRSS2 was found to block SARS-CoV-2 infection and might constitute a novel treatment option (Cell).

The attachment protein “spike” of the new coronavirus SARS-CoV-2 uses the same cellular attachment factor (ACE2) as SARS-CoV and uses the cellular protease TMPRSS2 for its activation. Existing, clinically approved drugs directed against TMPRSS2 inhibit SARS-CoV-2 infection of lung cells. Illustration: Markus Hoffmann

Several coronaviruses circulate worldwide and constantly infect humans, which normally caused only mild respiratory disease. Currently, however, we are witnessing a worldwide spread of a new coronavirus with more than 90,000 confirmed cases and over 3,000 deaths. The new virus has been named SARS coronavirus-2 and has been transmitted from animals to humans. It causes a respiratory disease called COVID-19 that may take a severe course. The SARS coronavirus-2 has been spreading since December 2019 and is closely related to the SARS coronavirus that caused the SARS pandemic in 2002/2003. No vaccines or drugs are currently available to combat these viruses.

Origin and transmission of pathogenic coronaviruses. Illustration: Markus Hoffmann

Moreover, their study suggests that antibody responses raised against SARS-CoV could at least partially protect against SARS-CoV-2 infection. These results have important implications for our understanding of SARS-CoV-2 transmissibility and pathogenesis and reveal a target for therapeutic intervention.

“Our results show that SARS-CoV-2 requires the protease TMPRSS2, which is present in the human body, to enter cells,” says Stefan Pöhlmann, head of the Infection Biology Unit at the German Primate Center. “This protease is a potential target for therapeutic intervention.”

The researchers demonstrated that SARS-CoV-2 uses the SARS55 CoV receptor, ACE2, for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Their results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

Since it is known that the drug camostat mesilate inhibits the protease TMPRSS2, the researchers further investigated whether the drug can also prevent infection with SARS-CoV-2. Their results also suggest that camostat mesilate might also protect against COVID-19.

“We have tested SARS-CoV-2 isolated from a patient and found that camostat mesilate blocks entry of the virus into lung cells,” says Markus Hoffmann, the lead author of the study. Camostat mesilate is a drug approved in Japan for use in pancreatic inflammation. “Our results suggest that camostat mesilate might also protect against COVID-19,” says Markus Hoffmann. “This should be investigated in clinical trials.”