MK-7845

**MK-7845** is a novel, reversible covalent inhibitor of the SARS-CoV-2 3CL protease (3CLPro, also known as Mpro), a viral enzyme essential for cleaving polyproteins into functional components required for replication. Developed by **Merck & Co., Inc.**, it features a unique difluorobutyl substituent at the P1 position that mimics glutamine and interacts with His163, offering improved solubility, absorption, and unboosted oral pharmacokinetics compared to typical amide-based inhibitors. MK-7845 demonstrates nanomolar potency (IC50 8.7 nM) against SARS-CoV-2 clinical subvariants and MERS-CoV, with >6 log reduction in lung viral load in K18-hACE2 and K18-hDPP4 mouse models when dosed orally, positioning it as a potential pan-coronavirus antiviral therapy.[1][2][5][8]