An anti-protease treatment against SARS-CoV-2?

Although effective vaccines against COVID-19 are now on the market, there remains an urgent need to find drugs for the treatment of serious cases, since those currently available are limited. In addition, since other epidemics involving coronaviruses have occurred over the last twenty years (MERS-CoV, SARS-CoV-1), it is also important to develop active treatments against all coronaviruses. SARS-CoV-2 possesses proteases, enzymes that cleave different viral proteins during their production by the cell’s machinery, an essential step for the manufacture of new viral particles. In this study, Pfizer laboratories have been testing a new candidate therapy against COVID-19, which blocks the Mpro protease.

At the time of the SARS-CoV-1 epidemic in 2002, a viral protease inhibitor was identified. Since the proteases of SARS-CoV-1 and 2 are very close, this inhibitor should also be active against the SARS-CoV-2 protease. The scientists tested this molecule in vitro (in cell culture). This protease inhibitor did not seem to be toxic for the cells since it did not inhibit the cellular proteases, which were too unlike coronavirus proteases. Regarding its antiviral activity, it seemed to be effective against several coronaviruses. The researchers then confirmed that this treatment was active against SARS-CoV-2 in vivo, using a mouse model.

So the Mpro protease inhibitor may be a candidate treatment for oral use against SARS-CoV-2. This type of inhibitor is already used against other viruses, such as HIV or the hepatitis C virus. Clinical studies on humans are now needed before this drug against SARS-CoV-2 and other coronaviruses can be licensed for use.