Dengue virus polyprotein (DENV polyprotein)

The Dengue virus (DENV) polyprotein is a single, large polypeptide that is post-translationally processed into three structural proteins (Capsid, Pre-membrane, and Envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [UniProt: P29978]. The structural proteins are vital for the assembly of the viral particle and its entry into host cells, whereas the non-structural proteins form the replication complex and assist in evading the host's innate immune system [PubMed: 28418843]. Specifically, the NS3 protein serves as a protease and helicase, and the NS5 protein acts as an RNA-dependent RNA polymerase and methyltransferase, making them the most prominent targets for antiviral drug development [PubMed: 31434747]. Therapeutic candidates like JNJ-1802 aim to disrupt the replication complex by targeting the NS3-NS4B interaction, while nucleoside analogs like Balapiravir target the NS5 polymerase [PubMed: 34616041]. Developing effective drugs against these proteins is complicated by the need for activity against all four DENV serotypes and the potential for antibody-dependent enhancement (ADE), which can exacerbate disease severity [WHO: Dengue Fact Sheet]. Despite these challenges, DENV proteins remain the primary focus for developing the first specific antiviral treatment for Dengue fever.

Other names

Dengue virus proteomeDENV structural and non-structural proteinsDengue virus genome polyproteinDENV-1/2/3/4 proteins

Inhibition of viral RNA-dependent RNA polymerase (RdRp), inhibition of NS2B-NS3 protease activity, disruption of the NS4B replication complex, and inhibition of viral entry or fusion.