The recent outbreak of SARS-CoV-2 is responsible for high morbidity and mortality rate across the globe. This requires an urgent identification of drugs and other interventions to overcome this pandemic. Computational drug repurposing represents an alternative approach to provide a more effective approach in search for COVID-19 drugs. Selected natural product known to have antiviral activities were screened, and based on their hits; a similarity search with FDA approved drugs was performed using computational methods. Obtained drugs from similarity search were assessed for their stability and inhibition against SARS-CoV-2 targets. Diosmin (DB08995) was found to be a promising drug that works with two distinct mechanisms, preventing viral replication and viral fusion into the host cell. Isoquercetin (DB12665) and rutin (DB01698) work by inhibiting viral replication and preventing cell entry, respectively. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that diosmin, isoquercetin, rutin and other similar flavone glycosides could serve as SARS-CoV-2 inhibitor, hence an alternative solution to treat COVID-19 upon further clinical validation.

最近爆​​发的 SARS-CoV-2 是造成全球高发病率和死亡率的原因。这需要紧急确定药物和其他干预措施来克服这种流行病。计算药物再利用代表了一种替代方法，可以提供一种更有效的方法来寻找 COVID-19 药物。筛选出已知具有抗病毒活性的选定天然产物，并基于它们的命中率；使用计算方法对 FDA 批准的药物进行相似性搜索。评估了从相似性搜索中获得的药物的稳定性和对 SARS-CoV-2 靶标的抑制作用。Diosmin (DB08995) 被发现是一种很有前途的药物，它具有两种不同的机制，即防止病毒复制和病毒融合到宿主细胞中。异槲皮素 (DB12665) 和芦丁 (DB01698) 分别通过抑制病毒复制和防止细胞进入发挥作用。我们基于分子动力学模拟和 MM-PBSA 结合自由能计算的分析表明，地奥司明、异槲皮素、芦丁和其他类似的黄酮苷可以作为 SARS-CoV-2 抑制剂，因此在进一步临床验证后可作为治疗 COVID-19 的替代解决方案.