RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic
| Autor: | Liang Chengyuan, Wenqiang Cao, Li Han, Li Jingyi, Xin YuWen, Jiayun Zhang, Xiaodong Ren, Jia Minyi, Taotao Qiang, Lei Tian, Minge Wan, Hong Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | European Journal of Medicinal Chemistry |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2021.113201 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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