Could a Japanese Encephalitis Drug Prevent COVID-19?

A drug known to inhibit a cellular protease TMPRSS2 could potentially be a novel therapeutic intervention for COVID-19 infections, according to German investigators who found that the cellular protein may allow entry of SARS-CoV-2 into lung cells.

Investigators in Germany took a step toward determining a potential novel therapeutic intervention for COVID-19 after identifying a cellular protein that may allow entry of SARS-CoV-2 into lung cells.

The research, published in the journal Cell, examined how SARS-CoV-2 enters human cells and found that a drug currently approved in Japan to treat pancreatic inflammation could block the COVID-19 infection.

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

The research team was led by infection biologists from the German Primate Centre and included investigators from 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.

The novel coronavirus is closely related to SARS-CoV, which emerged in 2002 and was stopped with measures including travel restrictions and patient isolation. The new study compared the 2 viruses and found similar properties and pandemic potential. Investigators noted that the spike protein (S protein) of the coronaviruses facilitates attachment to human cells through a 2-step process. SARS-CoV-2 depends on angiotensin-converting enzyme 2 (ACE2) for entry and serine protease TMPRSS2 for S protein priming. The study also determined that antibody responses raised by the earlier SARS-CoV could potentially provide partial protection against the novel virus, which may help control the outbreak.

Better understanding of the transmissibility and pathogenesis of SARS-CoV-2 brought investigators closer to a possible therapeutic intervention.

"We have tested SARS-CoV-2 isolated from a patient and found that camostat mesilate blocks entry of the virus into lung cells," lead author Markus Hoffmann, PhD, a researcher at the German Primate Center, said in the statement. "Our results suggest that camostat mesilate might also protect against COVID-19. This should be investigated in clinical trials."

Camostat mesilate is approved in Japan to treat pancreatic inflammation.

The study demonstrated that the drug blocked infection of human lung epithelial cells in culture. Human trials are necessary to prove whether the drug would be effective in stopping the infection.

As of Wednesday morning, there were more than 200,000 confirmed cases of COVID-19 worldwide resulting in more than 8,000 deaths as the pandemic continued to rapidly evolve.

US President Donald Trump issued new guidelines for slowing the spread of the disease, including staying home as much as possible and avoiding groups of 10 or more, discretionary travel, and eating at bars and restaurants.

On March 25, 2020, at 6PM ET, Contagion® is hosting a live CME webinar on what clinicians need to know amid the COVID-19 pandemic. Register here.