Viral polyprotein

A viral polyprotein is a large, singular polypeptide translated from a viral genome that serves as a precursor for multiple functional viral proteins. This strategy is extensively used by various virus families, including Coronaviridae, Flaviviridae, and Retroviridae, to maximize the coding efficiency of their compact genomes (UniProt, 2024). The polyprotein must be cleaved into smaller, active structural and non-structural proteins by specific viral or host proteases to facilitate viral replication and assembly. Because this proteolytic processing is essential for the production of infectious progeny, it represents a major vulnerability in the viral life cycle (NCBI Bookshelf, 2022). Antiviral drugs, specifically protease inhibitors, target the enzymes responsible for these cleavages, thereby preventing the maturation of viral proteins and effectively neutralizing the infection. This target is considered 'incorrect' in a strict sense because it is a broad category of precursor molecules across diverse viruses rather than a single specific protein, and the therapeutic focus is usually on the proteases that act upon it (PubMed, 2021).

Other names

Polyprotein precursorViral precursor proteinPolyproteinReplicase polyproteinGag-Pol polyproteinNon-structural polyprotein

Inhibition of proteolytic cleavage by targeting viral proteases (e.g., 3CLpro, NS3/4A, HIV Protease), which prevents the processing of the polyprotein into mature, functional viral proteins (StatPearls, 2023).