利用计算方法分析 SARS-CoV-2 RNA 依赖性 RNA 聚合酶作为潜在的治疗药物靶标。

Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach.

机构信息

Center of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, Pakistan.

Center for Advanced Studies in Agriculture and Food Security (CAS-AFS), University of Agriculture, Faisalabad, Pakistan.

出版信息

J Transl Med. 2020 Jul 7;18(1):275. doi: 10.1186/s12967-020-02439-0.

BACKGROUND

The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak.

METHODS

Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection.

RESULTS

Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2.

CONCLUSIONS

The anti-polymerase drugs predicted here-CID123624208 and CID11687749-may be considered for in vitro and in vivo clinical trials.

背景

起源于中国武汉的严重急性呼吸系统综合症相关冠状病毒 2 型（SARS-CoV-2）的爆发引起了全球健康关注，目前该大流行已在所有有人居住的大洲报告。迄今为止，尚无抗病毒药物可用于对抗这种病毒的爆发。

方法

考虑到情况的紧迫性，本研究旨在设计针对 SARS-CoV-2 的新药发现和/或重新定位策略。在本研究中，调节病毒复制的 RNA 依赖性 RNA 聚合酶（RdRp）被提议作为抑制病毒感染的潜在治疗靶标。

结果

对 SARS-CoV-2 的全基因组序列的进化研究表明，其与其他 SARS 病毒具有高度相似性（>90%）。通过抗病毒药物靶向 RdRp 的活性位点 ASP760 和 ASP761，可能是抑制冠状病毒 RdRp 从而抑制病毒复制的潜在治疗选择。基于靶标的虚拟筛选和分子对接结果表明，抗病毒药物 Galidesivir 及其结构类似物具有针对 SARS-CoV-2 的应用前景。