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联合计算机模拟和体外实验方法,鉴定出抗精神病药物鲁拉西酮和抗病毒药物 Elbasvir 是 SARS-CoV2 和 HCoV-OC43 的抑制剂。

Combined in silico and in vitro approaches identified the antipsychotic drug lurasidone and the antiviral drug elbasvir as SARS-CoV2 and HCoV-OC43 inhibitors.

机构信息

CNR-IBF, Istituto di Biofisica, Via Celoria 26, I-20133, Milano, Italy; Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, I-20133, Milano, Italy.

Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Regione Gonzole, 10, I-10043, Orbassano, Turin, Italy.

出版信息

Antiviral Res. 2021 May;189:105055. doi: 10.1016/j.antiviral.2021.105055. Epub 2021 Mar 10.

Abstract

The current emergency of the novel coronavirus SARS-CoV2 urged the need for broad-spectrum antiviral drugs as the first line of treatment. Coronaviruses are a large family of viruses that already challenged humanity in at least two other previous outbreaks and are likely to be a constant threat for the future. In this work we developed a pipeline based on in silico docking of known drugs on SARS-CoV1/2 RNA-dependent RNA polymerase combined with in vitro antiviral assays on both SARS-CoV2 and the common cold human coronavirus HCoV-OC43. Results showed that certain drugs displayed activity for both viruses at a similar inhibitory concentration, while others were specific. In particular, the antipsychotic drug lurasidone and the antiviral drug elbasvir showed promising activity in the low micromolar range against both viruses with good selectivity index.

摘要

当前新型冠状病毒 SARS-CoV2 的紧急情况促使人们需要广谱抗病毒药物作为一线治疗药物。冠状病毒是一个大家族的病毒,它们已经在至少另外两次爆发中对人类构成了挑战,并且很可能是未来的持续威胁。在这项工作中,我们开发了一个基于 SARS-CoV1/2 RNA 依赖性 RNA 聚合酶上已知药物的计算机对接的管道,结合了对 SARS-CoV2 和普通感冒人类冠状病毒 HCoV-OC43 的体外抗病毒测定。结果表明,某些药物在相似的抑制浓度下对两种病毒均显示出活性,而其他药物则具有特异性。特别是抗精神病药物鲁拉西酮和抗病毒药物 elbasvir 在低微摩尔范围内对两种病毒均显示出有希望的活性,且选择性指数良好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348e/7944860/22697adb311e/gr1_lrg.jpg

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