Dengue virus nonstructural protein 5 methyltransferase (DENV NS5 MTase)

The Dengue virus nonstructural protein 5 methyltransferase (DENV NS5 MTase) is the N-terminal domain of the multifunctional NS5 protein, which is the largest and most conserved protein in the Dengue virus genome (Source: PMC, 2014, 2017). It is responsible for the formation of the viral 5' RNA cap structure through sequential N7 and 2'-O methylations, utilizing S-adenosyl-L-methionine (SAM) as a methyl donor (Source: ResearchGate, 2021; PMC, 2010). This capping process is vital for protecting viral RNA from host exonucleases and ensuring efficient translation by the host cell machinery (Source: PMC, 2017). Additionally, the MTase domain plays a role in subverting the host's innate immune response by mimicking host mRNA capping patterns (Source: PMC, 2017). As an essential enzyme for viral replication, DENV NS5 MTase is a primary target for the development of direct-acting antivirals (Source: PubMed, 2025; PMC, 2021). Therapeutic strategies focus on small-molecule inhibitors that compete with SAM or block the RNA-binding site to halt the production of functional viral genomes (Source: PubMed, 2025; PMC, 2010). A major challenge in targeting this enzyme is achieving sufficient selectivity to avoid inhibiting human methyltransferases, which could lead to host toxicity (Source: J. Med. Chem., 2010).

Other names

NS5-MTaseDengue virus NS5 methyltransferase domainDENV MTaseS-adenosyl-L-methionine-dependent methyltransferase

Inhibition of N7 and 2'-O-methylation of the viral RNA cap by competing with S-adenosyl-L-methionine (SAM) or blocking the RNA binding site, thereby preventing viral mRNA stability and translation (Source: ResearchGate, 2021; PubMed, 2025).