Emerging RNA-centric technologies to probe RNA-protein interactions: importance in decoding the life cycle of positive sense single strand RNA viruses and antiviral discovery

Front Cell Infect Microbiol. 2025 May 21:15:1580337. doi: 10.3389/fcimb.2025.1580337. eCollection 2025.

Abstract

Positive sense single strand RNA (+ssRNA) viruses are one of the evolutionary successful organisms and many of them pose a significant threat to human health. Diseases caused by +ssRNA viruses such as COVID-19, Flu and acute viral hepatitis are major public health concern worldwide. Therefore, a lot of research is focused at decoding the life cycle of +ssRNA viruses and develop specific antiviral therapeutics against them. Interaction of the viral RNA with virus-encoded proteins and host proteins drives the lifecycle and pathogenesis of +ssRNA viruses. Recent developments in computational and high-throughput omics-based experimental technologies offer the sensitivity and specificity for molecular characterization of these RNA-protein complexes. These are promising tools to revolutionize the field of +ssRNA virus research and pave the way for antiviral discovery. This review summarizes the current scientific resources available to characterize the RNA-protein interactome of +ssRNA viruses and provides an overview of the drug discovery pipeline for developing antivirals against pathogenic +ssRNA viruses.

Keywords: RAP-MS; RNA binding protein; RNA-protein interactions; RaPID assay; positive strand RNA viruses.

Publication types

  • Review

MeSH terms

  • Antiviral Agents* / pharmacology
  • Drug Discovery / methods
  • Host-Pathogen Interactions
  • Humans
  • Positive-Strand RNA Viruses* / drug effects
  • Positive-Strand RNA Viruses* / genetics
  • Positive-Strand RNA Viruses* / metabolism
  • Positive-Strand RNA Viruses* / physiology
  • RNA, Viral* / genetics
  • RNA, Viral* / metabolism
  • RNA-Binding Proteins* / metabolism
  • SARS-CoV-2
  • Viral Proteins* / genetics
  • Viral Proteins* / metabolism

Substances

  • RNA, Viral
  • Antiviral Agents
  • Viral Proteins
  • RNA-Binding Proteins