Human coronavirus NL63 main protease (HCoV-NL63 Mpro) (HCoV-NL63 Mpro)

The Human coronavirus NL63 (HCoV-NL63) main protease, also known as 3C-like protease (3CLpro) or non-structural protein 5 (nsp5), is a vital enzyme for the replication and maturation of the HCoV-NL63 virus (UniProt: P0C6U5). HCoV-NL63 is an alphacoronavirus that causes respiratory tract illnesses, including the common cold and croup, particularly in children and immunocompromised individuals (PMID: 16254364). The protease functions as a homodimer and is responsible for cleaving the large viral polyproteins, pp1a and pp1ab, at eleven specific sites to release functional non-structural proteins required for the viral replication complex (PMID: 18417577). Because its substrate specificity—preferring a glutamine residue at the P1 position—is not shared by any known human proteases, it is considered an excellent target for selective antiviral drug development. Therapeutic candidates like GC376 and various peptidomimetics target the catalytic cysteine residue within the active site to block enzymatic activity and halt the viral life cycle (PMID: 32511330). Furthermore, the high degree of structural conservation of this protease across the Coronaviridae family makes it a key focus for the development of broad-spectrum antiviral agents.

Other names

3C-like protease3CLpronsp5Non-structural protein 5Main protease

Inhibition of the viral main protease (Mpro/3CLpro) prevents the cleavage of viral polyproteins pp1a and pp1ab into functional non-structural proteins, thereby arresting viral replication and assembly (PMID: 18417577).