The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic with more than 6.5 million deaths since 2019. Although a number of vaccines significantly reduced the mortality rate, a large number of the world population is yet being infected with highly contagious omicron variants/subvarints. Additional therapeutic interventions are needed to reduce hospitalization and curb the ongoing pandemic. The activity of the SARS-CoV-2 enzyme; chymotrypsin-like main protease (Mpro) is essential for the cleavage of viral nonstructural polypeptides into individual functional proteins and therefore Mpro is an attractive drug target. The aim of this review is to summarize recent progress toward the development of therapeutic drugs against Mpro protease.
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