Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp

Zhao, Jianyuan; Zhang, Yongxin; Wang, Minghua; Liu, Qian; Lei, Xiaobo; Wu, Meng; Guo, SaiSai; Yi, Dongrong; Li, Quanjie; Ma, Ling; Liu, Zhenlong; Guo, Fei; Wang, Jianwei; Li, Xiaoyu; Wang, Yucheng; Cen, Shan

[Image: see text] Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.