Existing Drug Inhibits SARS-CoV-2 Replication
Inside host cells, the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is translated into two polyproteins that are cleaved to give the individual viral proteins. The main viral protease, known as Mpro or 3CLpro, plays a key role in these cleavages, making it an important drug target.
Drayman et al. identified eight drugs that target 3CLpro from a library of 1,900 clinically safe drugs. Because of the challenge of working with SARS-CoV-2, they started by screening for drugs that inhibit the replication of a human coronavirus that causes the common cold. They then evaluated the top hits for inhibiting SARS-CoV-2 replication and for inhibiting 3CLpro.
Masitinib, a broad antiviral, inhibited the main proteases of coronaviruses and picornaviruses and was effective in reducing SARS-CoV-2 replication in mice.
Nir Drayman, et al. “Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2,” Science 373, 931-936 (2021). DOI: 10.1126/science.abg5827