Host proteases responsible for F0 cleavage

Host proteases responsible for F0 cleavage are a group of cellular enzymes, primarily including Furin and various Type II transmembrane serine proteases (TTSPs) like TMPRSS2, that are essential for the infectivity of many enveloped viruses (PubMed, PMID: 25135993). In viruses such as Respiratory Syncytial Virus (RSV) and other Paramyxoviruses, the fusion (F) protein is synthesized as an inactive F0 precursor that must be proteolytically processed into the disulfide-linked F1 and F2 subunits to become fusion-competent (UniProt, P03420). This cleavage event, often occurring at polybasic or monobasic motifs, exposes the fusion peptide, allowing the virus to merge its envelope with the host cell membrane (PubMed, PMID: 32155441). Because this process is strictly dependent on host machinery, these proteases represent attractive therapeutic targets for antiviral intervention, as seen with the use of serine protease inhibitors like camostat (PubMed, PMID: 32155441). Inhibiting these enzymes can effectively block viral entry and spread within the host. However, since these proteases also process vital endogenous proteins like growth factors and hormones, achieving therapeutic selectivity to avoid systemic toxicity remains a significant challenge (PubMed, PMID: 22508921).

Other names

F0-activating proteasesProprotein convertasesType II transmembrane serine proteasesFurin-like proteasesViral fusion protein processing enzymes

Inhibition of host-mediated proteolytic cleavage of the viral F0 precursor protein into F1 and F2 subunits, thereby preventing the conformational changes required for viral-cell membrane fusion and subsequent viral entry.