Year: 2026
Type: article
Abstract: Viral helicases are conserved nucleic acid-dependent ATPases that drive genome replication, gene expression, and virion assembly, thereby playing a central role in viral replication and pathogenicity. Here, we discuss structural, biochemical, and virological data to compare helicase superfamilies, their conserved motifs, and translocation models that couple ATP hydrolysis to strand separation. We then analyze how viral helicases regulate replication fork progression, transcription and translation of viral RNAs, viral genome remodeling during replication, genome-packaging strategies, and evasion of innate immune signaling. Mechanistic examples from picornaviruses, flaviviruses, herpesviruses, and coronaviruses demonstrate how helicase architecture, substrate specificity, and cofactors control these activities. Finally, we discuss the opportunities and drawbacks of targeting viral helicases with antiviral drugs, recent screening and structure-guided discovery efforts, and emerging resistance mechanisms. Overall, this review provides a virus-centered synthesis of helicase structure, function, and inhibition that links conserved enzymatic activities to diverse infection outcomes and antiviral strategies across viral families.
Source: Biomolecules
DOI: 10.3390/biom16020273
Authors: Gisoo Sarvari, David D. Boehr
Institution: Pennsylvania State University
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
Funder: National Institutes of Health
Award: G9000016779
OpenAlex ID: W7128400595