Key result
A viable nuclear localization signal mutant of the foot-and-mouth disease virus polymerase showed increased sensitivity to ribavirin mutagenesis, linked to the loop β9-α1 conformation.
NLS mutant boosts FMDV ribavirin sensitivity via RTP incorporation; hypothesis-generating for polymerase-targeted antivirals.
The nuclear localization signal (NLS) of the foot-and-mouth disease virus (FMDV) polymerase includes residues that modulate the sensitivity to mutagenic agents. Here we have described a viable NLS mutant with an amino acid replacement that facilitates virus extinction by ribavirin. The corresponding polymerase shows increased incorporation of ribavirin triphosphate and local structural modifications that implicate the template entry channel. Specifically, comparison of the structures of ribavirin-sensitive and ribavirin-resistant FMDV polymerases has identified loop β9-α11 conformation as a determinant of sensitivity to ribavirin mutagenesis.
No takes yet. Share an insight, caveat, or question.
Higuera et al. (2018) studied Foot-and-mouth disease virus (FMDV). Ribavirin was evaluated on Virus extinction and polymerase structural modifications. A viable nuclear localization signal mutant of the foot-and-mouth disease virus polymerase showed increased sensitivity to ribavirin mutagenesis, linked to the loop β9-α1 conformation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: