The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing
Xuqiao Hu,
Zhenru Zhou,
Fei Li,
Yang Xiao,
Zhaoyang Wang,
Jinfeng Xu,
Fajin Dong,
Hairong Zheng,
Rongmin Yu
Affiliations
Xuqiao Hu
Department of Ultrasound, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China
Zhenru Zhou
Department of Ultrasound, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Fei Li
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, SZ University Town, Shenzhen, 518055, China
Yang Xiao
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, SZ University Town, Shenzhen, 518055, China
Zhaoyang Wang
Department of Ultrasound, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Jinfeng Xu
Department of Ultrasound, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China; Corresponding author.
Fajin Dong
Department of Ultrasound, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China; Corresponding author.
Hairong Zheng
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, SZ University Town, Shenzhen, 518055, China; Corresponding author.
Rongmin Yu
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China; Department of Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China; Biotechnological Institute of Chinese Materia Medica, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China; Corresponding author.
Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2.16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg403, Tyr453, Trp495, Gly496, Phe497, Asn501and Tyr505) and ACE2 (Asn33, His34, Glu37, Asp38, Lys353, Ala386, Ala387, Gln388, Pro389, Phe390 and Arg393) complex.
