4.7 Review

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 213, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2021.113201

Keywords

COVID-19; RNA virus; SARS-CoV-2; RNA-dependent RNA polymerase (RdRp); Nucleoside/non-nucleoside analogue inhibitor

Funding

  1. National Natural Science Foundation of China [81602967, 81803784]
  2. China Postdoctoral Science Foundation [2016 M592898XB, 2019 M663921XB]
  3. Basic Research Program of Natural Science of Shaanxi Province [2019JQ-779, 2020CGXNG-044]
  4. Basic Research Plan of the Education Department of Shaanxi Province [19JC006]
  5. Key Scientific Research Group of Shaanxi Province [2020TD-009]
  6. Youth Innovation Team of Shaanxi Universities

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The RdRp enzyme, a therapeutic target for RNA virus infections, plays a crucial role in RNA synthesis. Promising RdRp inhibitors currently in studies offer potential for developing more effective anti-RNA virus drugs, which may be used for COVID-19 treatment in the current health emergency.
The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment. (C) 2021 Elsevier Masson SAS. All rights reserved.

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