Predicting the Animal Susceptibility and Therapeutic Drugs to SARS-CoV-2 Based on Spike Glycoprotein Combined With ACE2

作者：Min Shen, Chao Liu, Run Xu, Zijing Ruan, Shiying Zhao, Huidong Zhang, Wen Wang, Xinhe Huang, Yang Li, Yong Tang, Tai Yang, Xu Jia · 发表于：Frontiers in Genetics · 年份：2020 · DOI：10.3389/fgene.2020.575012 · 被引用次数：14 · 研究领域：SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies、Influenza Virus Research Studies

Recently, a few animals have been frequently reported to have been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether they are SARS-CoV-2 intermediate hosts is worthy of great attention. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from 10 kinds of animals. Results show that chimpanzees, domestic cats and cattles are more susceptible to infection by SARS-CoV-2. Cats in particular, such as pet cats and stray cats, interact very closely with humans, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic. Furthermore, based on ACE2(cats)-SARS-CoV-2-RBD model, through high-throughput screening methods using a pool of 30,000 small molecules, eight compounds were selected for binding free energy calculations. All the eight compounds can effectively interfere with the binding of ACE2 and Spike protein, especially Nelfinavir, providing drug candidates for the treatment and prevention of SARS-CoV-2, suggesting further assessment of the anti-SARS-CoV-2 activity of these compounds in cell culture. Although we only reported the results of the simulation, and more laboratory and epidemiological inv...