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April 6, 2023Frontiers in VirologyOpen Access

Regulation of viral RNA-dependent RNA polymerases by phosphorylation

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Why the study?

A better knowledge of viral RNA-dependent RNA polymerase phosphorylation is expected to facilitate the design of future antiviral drugs targeting polymerase activity.

Design

Review

Key result

Phosphorylation of viral RNA-dependent RNA polymerases by host kinases regulates viral RNA synthesis and represents a potential target for the design of future antiviral drugs.

Authors

CDCamille DuflosTMThomas Michiels

Discussion

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Overview

RdRp phosphorylation may guide host-directed antivirals; leaves open efficacy in clinical infection models.

Structured PICO

P
Population
RNA viruses (including flaviviruses, picornaviruses, coronaviruses, influenza viruses) and their RNA-dependent RNA polymerases (RdRps)
I
Intervention
Phosphorylation of RdRps by host kinases and phosphomimetic mutations
C
Comparator
Unphosphorylated state (wild-type or phosphoinhibiting mutations)
O
Outcome
Polymerase activity, RNA synthesis, and viral replication

Understanding the regulation of viral RNA-dependent RNA polymerases by host kinase-mediated phosphorylation may guide the development of novel antiviral therapies.

Limitations

  • Identification of specific phosphorylated residues often relies on in silico predictions and in vitro assays that are prone to false positives.
  • Overexpression models used to study phosphorylation lack the complexity of true viral infections.
  • Phosphomimetic and phosphoinhibitory mutations may affect local protein conformation independently of phosphorylation.

Cite This Study

Duflos et al. (2023) conducted a review in RNA virus infections. Phosphorylation of viral RNA-dependent RNA polymerases was evaluated. Phosphorylation of viral RNA-dependent RNA polymerases by host kinases regulates viral RNA synthesis and represents a potential target for the design of future antiviral drugs.

synapsesocial.com/papers/6a963f9e61dfe9432d01f2bchttps://doi.org/10.3389/fviro.2023.1176840
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