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筛选已知小分子以结合严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突糖蛋白上的血管紧张素转换酶2（ACE2）特异性受体结合域（RBD），用于重新利用以对抗2019冠状病毒病（COVID-19）。

screening of known small molecules to bind ACE2 specific RBD on Spike glycoprotein of SARS-CoV-2 for repurposing against COVID-19.

作者信息

Br Bharath, Damle Hrishikesh, Ganju Shiban, Damle Latha

机构信息

Computational Biology, Atrimed Biotech LLP, Banglore, 560100, India.

Atrimed Pharmaceuticals Pvt. Ltd, Banglore, 560001, India.

出版信息

F1000Res. 2020 Jul 1;9:663. doi: 10.12688/f1000research.24143.1. eCollection 2020.

DOI:10.12688/f1000research.24143.1
PMID:32765844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7385708/
Abstract

: Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. As no effective novel drugs are available currently, drug repurposing is an alternative intervention strategy. Here we present an   drug repurposing study that implements successful concepts of computer-aided drug design (CADD) technology for repurposing known drugs to interfere with viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates host cell entry via the hACE2 receptor. : A total of 4015 known and approved small molecules were screened for interaction with SARS-CoV-2-S through docking studies and 15 lead molecules were shortlisted. Additionally, streptomycin, ciprofloxacin, and glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability and affordability. The 18 molecules were subjected to molecular dynamics (MD) simulation. : The MD simulation results indicate that GA of plant origin may be repurposed for SARS-CoV-2 intervention, pending further studies. : Repurposing is a beneficial strategy for treating COVID-19 with existing drugs. It is aimed at using docking studies to screen molecules for clinical application and investigating their efficacy in inhibiting SARS-CoV-2-S. SARS-CoV-2-S is a key pathogenic protein that mediates pathogen-host interaction. Hence, the molecules screened for inhibitory properties against SARS-CoV-2-S can be clinically used to treat COVID-19 since the safety profile is already known.

摘要

人类冠状病毒（SARS-CoV-2）正在引发一场具有重大发病率和死亡率的大流行。由于目前尚无有效的新型药物，药物重新利用是一种替代干预策略。在此，我们展示了一项药物重新利用研究，该研究运用计算机辅助药物设计（CADD）技术的成功理念，将已知药物重新用于干扰病毒通过刺突糖蛋白（SARS-CoV-2-S）进入细胞，刺突糖蛋白通过hACE2受体介导宿主细胞进入。

通过对接研究，共筛选了4015种已知且已获批准的小分子与SARS-CoV-2-S的相互作用，并入围了15种先导分子。此外，根据链霉素、环丙沙星和甘草酸（GA）已报道的抗病毒活性、安全性、可获得性和可承受性对其进行了选择。对这18种分子进行了分子动力学（MD）模拟。

MD模拟结果表明，植物来源的GA可能可重新用于SARS-CoV-2干预，有待进一步研究。

重新利用是用现有药物治疗COVID-19的有益策略。其目的是利用对接研究筛选用于临床应用的分子，并研究它们抑制SARS-CoV-2-S的功效。SARS-CoV-2-S是介导病原体与宿主相互作用的关键致病蛋白。因此，筛选出的对SARS-CoV-2-S具有抑制特性的分子可用于临床治疗COVID-19，因为其安全性已为人所知。

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