Atomic resolution of the broad-spectrum antiviral drug cascade to facilitate the design of antiviral drugs (IMAGE)

PLOS

Atomic resolution of the broad-spectrum antiviral drug cascade to facilitate the design of antiviral drugs

Caption

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/)

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Credit must be given to the creator.

License

CC BY

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