Viral 3CLpro as a Target for Antiviral Intervention Using Milk-Derived Bioactive Peptides

Viruses of the picornavirus-like supercluster mainly achieve cleavage of polyproteins into mature proteins through viral 3-chymotrypsin proteases (3Cpro) or 3-chymotrypsin-like proteases (3CLpro). Due to the essential role in processing viral polyproteins, 3Cpro/3CLpro is a drug target for treating viral infections. The 3CLpro is considered the main protease (Mpro) of coronaviruses. In the current study, the SARS-CoV-2 Mpro inhibitory activity of di- and tri-peptides (DTPs) resulted from the proteolysis of bovine milk proteins was evaluated. A set of 326 DTPs were obtained from virtual digestion of bovine milk major proteins. The resulted DTPs were screened using molecular docking. Twenty peptides (P1–P20) showed the best binding energies (ΔGb