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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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An update on inhibitors targeting RNA-dependent RNA polymerase for COVID-19 treatment: Promises and challenges

Xiaoying Xu1, Yuheng Chen2, Xinyu Lu3

  • 1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Biochemical Pharmacology
|October 9, 2022
PubMed

Insights

This review explores RNA-dependent RNA polymerase (RdRp) inhibitors as potential COVID-19 therapeutics. It analyzes inhibitor interactions and effectiveness, proposing strategies for developing new antiviral drugs against SARS-CoV-2 variants.

Area of Science:

  • Virology
  • Drug Discovery
  • Structural Biology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates urgent development of effective therapeutic drugs.
  • Highly transmissible SARS-CoV-2 variants continue to drive global infection waves.
  • RNA-dependent RNA polymerase (RdRp) is a conserved and essential viral enzyme, making it a prime target for antiviral therapies.

Purpose of the Study:

  • To review recent advancements in the study of RNA-dependent RNA polymerase (RdRp) inhibitors.
  • To analyze the structural interactions between RdRp inhibitors and the enzyme complex.
  • To evaluate the effectiveness of current RdRp inhibitors and propose future development strategies.

Main Methods:

  • Literature review of studies on RdRp inhibitors.
  • Analysis of structural data detailing inhibitor-enzyme interactions.
  • Assessment of inhibitor efficacy against SARS-CoV-2.

Main Results:

  • RdRp is a highly conserved enzyme across coronaviruses and a promising target for antiviral drug development.
  • Structural analysis reveals key interactions between inhibitors and the RdRp enzyme complex.
  • Current inhibitors show varying degrees of effectiveness, highlighting the need for improved strategies.

Conclusions:

  • RdRp inhibitors represent a critical avenue for combating COVID-19.
  • Understanding structural interactions is key to designing potent and specific inhibitors.
  • Further research into novel strategies is essential for developing next-generation SARS-CoV-2 therapeutics.
Keywords:
AntiviralCOVID-19InhibitorsRdRpSARS-CoV-2

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