由严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)引起的2019年冠状病毒病(COVID-19)已经杀死了数百万人,并继续在全球范围内造成严重破坏。这种突然而致命的大流行强调了开发抗病毒药物的必要性,这种药物可以迅速施用以降低发病率,死亡率,和病毒传播。因此,缺乏有效的抗COVID-19治疗,特别是考虑到自SARS-CoV-2爆发以来,漫长的药物开发过程以及与SARS-CoV-2相关的关键死亡工具,药物再利用(或重新定位)构成了迄今为止,减轻病毒传播的理想和现成的最佳方法,包含感染,并降低COVID-19相关死亡率。的确,基于SARS-CoV-2与以前的冠状病毒(CoV)的分子相似性方法,据报道,重新利用的药物会阻碍SARS-CoV-2的复制。因此,了解病毒复制的抑制机制,通过重新利用抗病毒药物和已知阻断CoV和SARS-CoV-2增殖的化学品是至关重要的,它为特定的治疗选择和COVID-19疗法开辟了道路。在这次审查中,我们强调了针对SARS-CoV-2的药物再利用策略的分子基础。值得注意的是,我们讨论了病毒复制的抑制机制,涉及并包括抑制SARS-CoV-2蛋白酶(3C样蛋白酶,3CLpro或木瓜蛋白酶样蛋白酶,PLpro)通过蛋白酶抑制剂,例如Carmofur,Ebselen,和GRL017,聚合酶(RNA依赖性RNA聚合酶,RdRp)通过苏拉明这样的药物,Remdesivir,或者Favipiravir,和蛋白质/肽抑制病毒细胞融合和宿主细胞复制途径,比如双硫仑,GC376和Molnupiravir.如果适用,与已批准临床使用的SARS-CoV抑制剂进行了比较,以提供进一步的见解,以了解抑制SARS-CoV-2复制的分子基础,并为未来的药物发现研究得出结论.
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to wreak havoc across the globe. This sudden and deadly pandemic emphasizes the necessity for anti-viral drug development that can be rapidly administered to reduce morbidity, mortality, and virus propagation. Thus, lacking efficient anti-COVID-19 treatment, and especially given the lengthy drug development process as well as the critical death tool that has been associated with SARS-CoV-2 since its outbreak, drug repurposing (or repositioning) constitutes so far, the ideal and ready-to-go best approach in mitigating viral spread, containing the infection, and reducing the COVID-19-associated death rate. Indeed, based on the molecular similarity approach of SARS-CoV-2 with previous coronaviruses (CoVs), repurposed drugs have been reported to hamper SARS-CoV-2 replication. Therefore, understanding the inhibition mechanisms of viral replication by repurposed anti-viral drugs and chemicals known to block CoV and SARS-CoV-2 multiplication is crucial, and it opens the way for particular treatment options and COVID-19 therapeutics. In this review, we highlighted molecular basics underlying drug-repurposing strategies against SARS-CoV-2. Notably, we discussed inhibition mechanisms of viral replication, involving and including inhibition of SARS-CoV-2 proteases (3C-like protease, 3CLpro or Papain-like protease, PLpro) by protease inhibitors such as Carmofur, Ebselen, and GRL017, polymerases (RNA-dependent RNA-polymerase, RdRp) by drugs like Suramin, Remdesivir, or Favipiravir, and proteins/peptides inhibiting virus-cell fusion and host cell replication pathways, such as Disulfiram, GC376, and Molnupiravir. When applicable, comparisons with SARS-CoV inhibitors approved for clinical use were made to provide further insights to understand molecular basics in inhibiting SARS-CoV-2 replication and draw conclusions for future drug discovery research.