image: Bemnifosbuvir, a guanosine analogue, is in clinical trials against the Hepatitis C virus (HCV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This compound undergoes a series of five cellular modifications to transform into its active triphosphate form, AT-9010. The rate-limiting step in the activation pathway involves the histidine triad nucleotide phosphoramidase (HINT1). Structural analysis reveals that HINT1, when complexed with the Bemnifosbuvir intermediate (AT-8003), exhibits an unusual binding mode distinct from that of natural nucleotides, providing an explanation for the observed rate limitation. Red drug pill, patient and virus-sketch icons by Marcel Tisch is licensed under CC0 https://creativecommons.org/publicdomain/zero/1.0/
Credit: François Ferron (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)
Atomic resolution of the broad-spectrum antiviral drug cascade to facilitate the design of antiviral drugs
In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002743
Article Title: The activation cascade of the broad-spectrum antiviral bemnifosbuvir characterized at atomic resolution
Author Countries: France, United States, Germany
Funding: see manuscript
Journal
PLOS Biology
Method of Research
Observational study
Subject of Research
Cells
COI Statement
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S.G., A.M. and J.P.S. are employees of ATEA Pharmaceuticals, Inc.