Identification and Characterization of a Metal Binding-Independent Rift Valley Fever Virus Endonuclease Inhibitor.

ABSTRACT: The viral cap-snatching mechanism, facilitated by the endonuclease (EndoN) domain of viral polymerases, is critical for viral gene transcription and translation and is therefore an attractive target for antiviral development. The successful development of EndoN inhibitor XOFLUZA (Baloxavir marboxil) has opened the possibility that the EndoN domain of negative-sense RNA viruses (NSVs) can be targeted in a similar fashion. Rift Valley Fever Virus (RVFV) belongs to the Bunyaviricetes class, which includes other pathogens with pandemic potential, such as severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). Here, we identify MBXC-4522 as a RVFV EndoN inhibitor using a high-throughput FRET-based assay. We screened a library of >20,000 compounds and identif

SUBMITTER: Kirby CD 

PROVIDER: S-EPMC12442054 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature