Human coronavirus OC43 3C-like protease (3CLpro)

The Human coronavirus OC43 3C-like protease (hCoV-OC43 3CLpro), also known as the main protease (Mpro) or non-structural protein 5 (nsp5), is an essential enzyme for the life cycle of the hCoV-OC43 virus [1, 2]. As a cysteine protease, it functions as a homodimer and is responsible for the proteolytic processing of the viral polyproteins pp1a and pp1ab into functional non-structural proteins [1, 8]. This cleavage is a prerequisite for the assembly of the viral replication-transcription complex, making the enzyme indispensable for viral replication [4, 10]. hCoV-OC43 is a major cause of the common cold and can lead to more severe respiratory tract infections in vulnerable populations [13, 14]. Due to its critical role and high conservation among coronaviruses, 3CLpro is a primary target for the development of broad-spectrum antiviral therapeutics [1, 8]. Drugs such as nirmatrelvir and various experimental peptidomimetics interact with the enzyme's active site, often forming covalent bonds with the catalytic cysteine residue to inhibit its activity [2, 8]. Successful inhibition of this protease effectively halts the production of new viral particles, providing a robust mechanism for treating coronavirus infections [4, 11].

Other names

Main proteaseMpro3CL proteaseNon-structural protein 5nsp5C30 endopeptidase

Inhibition of viral polyprotein cleavage by binding to the active site of the 3C-like protease, thereby preventing the maturation of non-structural proteins and halting viral replication.