Yellow fever virus polyprotein (YFV polyprotein)

The Yellow fever virus polyprotein is a large precursor protein translated from the single-stranded positive-sense RNA genome of the Yellow fever virus (YFV), a member of the Flaviviridae family (UniProt P03314). This polyprotein is co- and post-translationally processed by both host and viral proteases into three structural proteins (C, prM, and E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (PubMed: 29165208). The structural proteins form the viral particle, while the non-structural proteins are responsible for genome replication, polyprotein processing, and modulating the host immune response. Key enzymatic components within the polyprotein, such as the NS3 protease/helicase and the NS5 RNA-dependent RNA polymerase, are essential for the viral life cycle and serve as primary targets for antiviral drug discovery (PubMed: 30534445). Although a highly effective vaccine exists, there are currently no approved specific antiviral therapies for yellow fever, making the polyprotein a critical focus for developing small-molecule inhibitors to treat active infections (NIH: Yellow Fever). Drugs like Sofosbuvir and Galidesivir have been studied for their ability to inhibit the NS5 polymerase component of the polyprotein (PubMed: 28356511). Targeting the polyprotein aims to reduce viral load and prevent the progression of the disease to its toxic hemorrhagic phase. Challenges in targeting this protein include the high mutation rate of RNA viruses and the need for high specificity to avoid host cell toxicity.

Other names

Genome polyproteinYFV-PPPolyproteinYFV-GP

Inhibition of RNA-dependent RNA polymerase (NS5) and viral protease (NS3) to block viral replication and maturation.