F01

F01 is a small molecule, non-covalent inhibitor of the SARS-CoV-2 3C-like protease (3CLpro), also known as the main protease (Mpro). It was identified through NMR-based fragment screening and subsequent optimization by researchers at the Shanghai Institute of Materia Medica. F01 is characterized by its unique binding mode, which involves the opening and occupancy of a previously uncharacterized induced-fit pocket designated as S2*. This specific interaction provides high selectivity for the viral protease over human cysteine proteases such as cathepsin L and cathepsin K, potentially minimizing off-target toxicity. By inhibiting 3CLpro, F01 prevents the processing of viral polyproteins essential for replication, thereby demonstrating antiviral activity against SARS-CoV-2. It serves as a chemical lead for the development of more potent inhibitors like F02.