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Development of a Simple <i>In Vitro</i> Assay To Identify and Evaluate Nucleotide Analogs against SARS-CoV-2 RNA-Dependent RNA Polymerase

Gaofei Lu, Xi Zhang, Weinan Zheng, Jialei Sun, Lan Hua, Lan Xu, Xin‐Jie Chu, Sheng Ding, Wen Xiong

2020Antimicrobial Agents and Chemotherapy29 citationsDOIOpen Access PDF

Abstract

Nucleotide analogs targeting viral RNA polymerase have been proved to be an effective strategy for antiviral treatment and are promising antiviral drugs to combat the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we developed a robust in vitro nonradioactive primer extension assay to quantitatively evaluate the efficiency of incorporation of nucleotide analogs by SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Our results show that many nucleotide analogs can be incorporated into RNA by SARS-CoV-2 RdRp and that the incorporation of some of them leads to chain termination.

Topics & Concepts

RNARNA polymeraseIn vitroSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)RNA-dependent RNA polymeraseNucleotideVirologyPolymeraseBiologyComputational biologyCoronavirus disease 2019 (COVID-19)GeneticsMedicineDNAGeneInfectious disease (medical specialty)PathologyDiseaseSARS-CoV-2 and COVID-19 ResearchViral gastroenteritis research and epidemiologySARS-CoV-2 detection and testing