# Structure, Function and Inhibition of Helicases Involved in Virus Infection

## TL;DR

This paper reviews the structure, function, and inhibition of viral helicases, which are crucial for virus replication and potential drug targets.

## Contribution

The paper provides a virus-centered synthesis linking helicase enzymatic activities to diverse infection outcomes and antiviral strategies.

## Key findings

- Viral helicases play central roles in replication, gene expression, and virion assembly.
- Helicase architecture, substrate specificity, and cofactors control replication and immune evasion.
- Targeting helicases with antivirals shows promise but faces resistance and drug design challenges.

## 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.