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Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.

Siyuan Zhao1, Ziyu Lin1, Minglian Wang1

  • 1College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.

Molecules (Basel, Switzerland)
|June 26, 2026
PubMed
Summary
This summary is machine-generated.

Developing effective antiviral drugs is crucial as RNA viruses like SARS-CoV-2 mutate rapidly. This study reviews RNA-dependent RNA polymerase (RdRp) as a broad-spectrum target and methods for its activity assay to aid drug development.

Keywords:
RNA-dependent RNA polymerase (RdRp)RdRp assayRdRp inhibitorpositive-stranded RNA virus

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Area of Science:

  • Virology
  • Drug Discovery
  • Biochemistry

Background:

  • Positive-strand RNA viruses (e.g., SARS-CoV-2, DENV) pose global health threats due to high infectivity and mutation rates.
  • Limited availability of specific and effective antiviral therapies necessitates novel drug development strategies.

Purpose of the Study:

  • To review the structural characteristics of RNA-dependent RNA polymerase (RdRp), a conserved enzyme essential for viral replication.
  • To summarize methods for constructing RdRp activity assays, particularly cell-free assays, for antiviral drug screening.
  • To provide an overview of existing RdRp inhibitors and their development status.

Main Methods:

  • Literature review of RdRp structure and function.
  • Compilation of various RdRp activity assay methodologies, focusing on cell-free systems.
  • Survey of reported RdRp inhibitors and their preclinical/clinical progress.

Main Results:

  • RdRp is a highly conserved, virus-specific enzyme, making it an ideal target for broad-spectrum antiviral drugs.
  • Established RdRp activity assays, especially cell-free assays, are vital for efficient drug screening and development.
  • Several RdRp inhibitors are under investigation, showing promise for future antiviral therapies.

Conclusions:

  • RdRp represents a significant and druggable target for developing novel antiviral agents against a wide range of RNA viruses.
  • The development and application of RdRp activity assays are critical for accelerating the discovery of effective antiviral drugs.
  • Further research into RdRp inhibitors is essential to combat the ongoing threat of RNA viral infections.