Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase

Tiantian Xu1,2, Lu Zhang1,2,3

  • 1State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.

Insights

Nucleoside analogs show promise in inhibiting SARS-CoV-2 replication by targeting the viral RNA-dependent RNA polymerase (RdRp). This review summarizes experimental findings and molecular mechanisms for developing new antiviral drugs.

Area of Science:

  • Virology
  • Medicinal Chemistry
  • Structural Biology

Background:

  • The COVID-19 pandemic necessitates novel antiviral therapeutics targeting SARS-CoV-2.
  • The viral RNA-dependent RNA polymerase (RdRp) is crucial for viral replication and a key target for drug development.
  • Nucleoside analogs, mimicking natural substrates, are promising inhibitors of SARS-CoV-2 RdRp.

Purpose of the Study:

  • To review nucleoside analogs demonstrating experimental inhibition of SARS-CoV-2 RdRp.
  • To elucidate the molecular mechanisms of nucleoside analog action against SARS-CoV-2 RdRp.
  • To guide the rational design of antiviral medications and research into viral transcription.

Main Methods:

  • Literature review of experimental investigations on nucleoside analogs targeting SARS-CoV-2 RdRp.
  • Analysis of structural biology and computational research findings.
  • Classification of inhibitory mechanisms based on recent studies.

Main Results:

  • Compilation of nucleoside analogs with proven inhibitory effects on SARS-CoV-2 RdRp.
  • Detailed examination of molecular mechanisms, including structural insights.
  • Categorization of inhibition strategies based on experimental and computational data.

Conclusions:

  • Nucleoside analogs are effective inhibitors of SARS-CoV-2 RdRp.
  • Understanding molecular mechanisms is key to optimizing antiviral drug design.
  • This review provides a foundation for future research in antiviral therapies and viral mechanisms.

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