1. RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic
- Author
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Liang Chengyuan, Wenqiang Cao, Li Han, Li Jingyi, Xin YuWen, Jiayun Zhang, Xiaodong Ren, Jia Minyi, Taotao Qiang, Lei Tian, Minge Wan, and Hong Liu
- Subjects
RNA virus ,Antagonists & inhibitors ,viruses ,Allosteric regulation ,RNA-dependent RNA polymerase ,Review Article ,Antiviral Agents ,01 natural sciences ,Virus ,03 medical and health sciences ,chemistry.chemical_compound ,RNA polymerase ,Drug Discovery ,Animals ,Humans ,Enzyme Inhibitors ,Pandemics ,030304 developmental biology ,chemistry.chemical_classification ,Pharmacology ,Nucleoside/non-nucleoside analogue inhibitor ,0303 health sciences ,Coronavirus RNA-Dependent RNA Polymerase ,biology ,SARS-CoV-2 ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Drug Repositioning ,COVID-19 ,RNA ,Nucleosides ,General Medicine ,biology.organism_classification ,Virology ,RNA-dependent RNA polymerase (RdRp) ,COVID-19 Drug Treatment ,0104 chemical sciences ,Enzyme - Abstract
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., Graphical abstract Image 1, Highlights • This article provides an overview of RdRp inhibitors that have been launched or are in clinical studies for the treatment of RNA virus infections, including COVID-19. • Nucleoside inhibitors (NIs) exhibit broad-spectrum antiviral activity but pose a more serious toxicity risk than non-nucleoside inhibitors (NNIs) because high dosages of NIs result in accumulation in plasma. • Structurally diverse NNIs are endowed with high potential activities but tend to induce drug resistance due to the RdRp allosteric site.
- Published
- 2021
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