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Abstract：
In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, over 21 million people have been infected, with more than 750.000 casualties. Today, no vaccine or antiviral drug is available. While the development of a vaccine might take at least a year, and for a novel drug, even longer; finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a docking-based screening using a quantum mechanical scoring of a library built from approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins. Following the analysis of our structure-based compound screening, we propose several structurally diverse compounds (either FDA-approved or in clinical trials) that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.
摘要：
2019年12月，由冠状病毒SARS-CoV-2引起的传染病在武汉出现，中国。这种疾病（COVID-19）在世界范围内迅速传播，并于2020年3月被世界卫生组织（WHO）宣布为大流行。今天,超过2100万人被感染，伤亡人数超过750.000。今天,没有疫苗或抗病毒药物可用。虽然疫苗的开发可能需要至少一年的时间，对于一种新型药物，甚至更长；找到旧药的新用途（药物再利用）可能是最有效的策略。我们提出了一种基于对接的筛选，使用量子力学评分的库，该库由批准的药物和正在进行临床试验的化合物建立，针对三种SARS-CoV-2靶蛋白：刺突或S蛋白，和两种蛋白酶,主要蛋白酶和木瓜蛋白酶样蛋白酶。S蛋白直接与人宿主细胞表面的血管紧张素转换酶2受体结合，而这两种蛋白酶处理病毒多蛋白。在我们基于结构的化合物筛选分析之后，我们提出了几种结构上不同的化合物（FDA批准或临床试验），它们可以显示出对SARS-CoV-2的抗病毒活性。显然,这些化合物应在实验测定和临床试验中进一步评估，以确认它们对疾病的实际活性。我们希望这些发现可能有助于合理设计针对COVID-19的药物。
