Target-Based Virtual Screening and LC/MS-Guided Isolation Procedure for Identifying Phloroglucinol-Terpenoid Inhibitors of SARS-CoV-2

• DOI: 10.1021/acs.jnatprod.1c00805
• Publication Date: 2022-01-27T15:30:50Z
• Authors: Bo Hou; Yu-Min Zhang; Han-Yi Liao; Li-Feng Fu; De-Dong Li; Xin Zhao; Jian-Xun Qi; Wei Yang; Geng-Fu Xiao; Lian Yang; Zheng-Yu Zuo; Lin Wang; Xiang-Lei Zhang; Fang Bai; Liu Yang; George F. Gao; Hao Song; Jiang-Miao Hu; Wei-Juan Shang; Jun Zhou
• Keywords: Phloroglucinol; Vero cell; Natural product; Coronavirus; Docking (animal); Drug repositioning

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide date. Due the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied identify novel and high-content compounds 1–4 inhibitory effects on SARS-CoV-2 in Vero E6 cells from plant Dryopteris wallichiana. These were also evaluated against Calu-3 showed unambiguous activity. inhibition assay of targets that 3 4 mainly inhibited 3CLpro, effective Kd values. Through docking molecular dynamics modeling, binding site is described, providing a comprehensive understanding 3CLpro interactions for 3, including hydrogen bonds, hydrophobic spatial occupation B ring. Compounds represent new, potential lead development anti-SARS-CoV-2 drugs. This study method exploring potency natural products identifying bioactive possible COVID-19 treatment.