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抗 HCV,核苷酸抑制剂,重新用于 COVID-19。

Anti-HCV, nucleotide inhibitors, repurposing against COVID-19.

机构信息

Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt; College of Applied Medical Sciences, University of Al-Jouf, Saudi Arabia.

出版信息

Life Sci. 2020 May 1;248:117477. doi: 10.1016/j.lfs.2020.117477. Epub 2020 Feb 28.

Abstract

AIMS

A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp).

MATERIALS AND METHODS

In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin.

KEY FINDINGS

The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease.

SIGNIFICANCE

The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.

摘要

目的

两个月前在中国武汉报告了一种新出现的人类冠状病毒(HCoV)(COVID-19)。截至今天,在中国和其他 40 个国家报告的 8 万例确诊病例中,已有超过 2700 人死亡。一个月前中国证实 COVID-19 可在人与人之间传播。根据世界卫生组织(WHO)的报告,SARS HCoV 负责 8000 多例确诊病例,其中 774 例死亡。此外,MERS HCoV 负责报告的约 2500 例中的 858 例死亡。本研究旨在测试抗 HCV 药物对 COVID-19 RNA 依赖的 RNA 聚合酶(RdRp)的作用。

材料和方法

在这项研究中,我们使用序列分析、建模和对接来构建武汉 COVID-19 RdRp 的模型。此外,针对新出现的武汉 HCoV RdRp 模型,我们选择了包括已批准药物 Sofosbuvir 和 Ribavirin 在内的抗聚合酶药物进行靶向研究。

主要发现

结果表明,Sofosbuvir、IDX-184、Ribavirin 和 Remidisvir 作为针对新出现的 HCoV 疾病的有效药物。

意义

本研究为 COVID-19 RdRp 提供了一个完美的模型,使其能够在计算机上针对抗聚合酶药物进行测试。此外,该研究还提出了一些先前已证明对新出现的病毒感染有效的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca59/7089605/dd682b930d01/gr1a_lrg.jpg

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