Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and Efficacy In Vivo.

ABSTRACT: Every year, dengue virus (DENV) causes one hundred million infections worldwide that can result in dengue disease and severe dengue. Two other mosquito-borne flaviviruses, i.e., Zika virus (ZIKV) and West Nile virus (WNV), are responsible of prolonged outbreaks and are associated with severe neurological diseases, congenital defects, and eventually death. These three viruses, despite their importance for global public health, still lack specific drug treatments. Here, we describe the structure-guided discovery of small molecules with pan-flavivirus antiviral potential by a virtual screening of ~1 million structures targeting the NS3-NS5 interaction surface of different flaviviruses. Two molecules inhibited the interaction between DENV NS3 and NS5 in vitro and the replication of all

SUBMITTER: Celegato M 

PROVIDER: S-EPMC9973282 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature