Bunyaviral Cap-Snatching Endonuclease Activity and Inhibition with Baloxavir-like Inhibitors in the Context of Full-Length L Proteins.

ABSTRACT: The Bunyavirales order includes a range of zoonotic viruses, which can cause severe disease in humans. The viral replication machinery is a logical target for the development of direct-acting antivirals. Inhibition of the cap-snatching endonuclease activity of related influenza viruses provides a proof of concept. Using the influenza B virus (IBV) RNA-dependent RNA polymerase complex as a benchmark, we conducted a comparative analysis of endonuclease activities of recombinant full-length bunyaviral L proteins using gel-based assays. The IBV complex demonstrates specific endonucleolytic cleavage and a clear preference for capped substrates. In contrast, severe fever with thrombocytopenia syndrome, Sin Nombre, and Hantaan virus L proteins readily cleave capped and uncapped RNAs to a b

SUBMITTER: Loutan AJ 

PROVIDER: S-EPMC11946187 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature