A novel screening strategy of anti-SARS-CoV-2 drugs via blocking interaction between Spike RBD and ACE2. (February 2021)

• Record Type: Journal Article
• Authors: Wang, Xiaoning; Yang, Chuanxi; Sun, Yangyang; Sui, Xin; Zhu, Tong; Wang, Qian; Wang, Shuai; Yang, Jun; Yang, Weijie; Liu, Fengying; Zhang, Minmin; Wang, Yongan; Luo, Yuan
• Is Part Of: Environment international. Volume 147(2021)
• Publication Date: 2021-02
• Subjects: SARS-CoV-2 Spike RBD -- hACE2 -- Blockade mechanism -- Structure-activity relationship -- Anti-SARS-CoV-2 drugs screening strategy; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2020.106361
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Drug property and binding energy were negative correlation for compounds. 8 kinds of common structures with high anti-SARS-CoV-2 activity were selected. The structure-activity relationship between drugs and SARS-CoV-2 therapy was built. This is the first study on screening strategy of anti-SARS-CoV-2 drugs. Abstract: Corona virus disease 2019 has spread worldwide, and appropriate drug design and screening activities are required to overcome the associated pandemic. Using computational simulation, blockade mechanism of SARS-CoV-2 spike receptor binding domain (S RBD) and human angiotensin converting enzyme 2 (hACE2) was clarified based on interactions between RBD and hesperidin. Interactions between anti-SARS-CoV-2 drugs and therapy were investigated based on the binding energy and druggability of the compounds, and they exhibited negative correlations; the compounds were classified into eight common types of structures with highest activity. An anti-SARS-CoV-2 drug screening strategy based on blocking S RBD/hACE2 binding was established according to the first key change (interactions between hesperidin and S RBD/hACE2) vs the second key change (interactions between anti-SARS-CoV-2 drugs and RBD/hACE2) trends. Our findings provide valuable information on the mechanism of RBD/hACE2 binding and on the associated screening strategies for anti-SARS-CoV-2 drugs based on blocking mechanisms of pockets.