抗hiv和抗hcv药物被认为是SARS - CoV-2 (COVID-19) rna依赖性rna聚合酶NSP12活性的抑制剂

F. Athar, Amjad Beg
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引用次数: 28

摘要

冠状病毒是一种新兴的传染性病毒,自2003年的非典和2013年的中东呼吸综合征以来,它一直在威胁着世界。2019年,当一种新型冠状病毒在中国武汉出现并感染当地人群时,这种病毒再次以其强劲的大流行震惊了全世界。被命名为SARS CoV-2的病毒和由这种传染性病毒引起的疾病被介绍为COVID - 19。自2019年12月以来,这种病毒在全球夺走了432,973人的生命。本研究阐述了HIV和HCV药物在靶向SARS CoV 2中负责RNA依赖性RNA聚合酶活性的nsp12基因中的作用。采用同源性建模、结构验证和分子对接分析等方法评价NSP12 (RdRp)蛋白与HIV/HCV药物的结合亲和力和相互作用分析。研究结果影响了抗hiv中的奈非那韦(NFV)、雷替格雷韦(RAL)和德拉韦丁(DLV)以及抗hcv中的帕利他韦(PTV)、贝拉布韦(BCV)和来地帕韦(LDV)作为SARS CoV-2 RdRp三元复合物最有效的抑制剂的作用。这些药物与存在于病毒RdRp活性位点的残基具有很强的结合亲和力,这些残基是病毒复制所必需的。这项研究为治疗发展方向提供了重要信息,因为我们正在处理迫切需要药物或疫苗来对抗COVID-19的情况。因此,这项研究为FDA批准的抗病毒药物提供了基本的分子信息,这些药物可用于治疗这种疾病。重要的是,列出的药物从未优先考虑其对COVID-19的有效性。免疫缺陷病毒(HIV)药物、丙型肝炎病毒(HCV)药物和抗疟疾药物。18、19
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Anti-HIV and Anti-HCV drugs are the putative inhibitors of RNA-dependent-RNA polymerase activity of NSP12 of the SARS CoV-2 (COVID-19)
Corona virus is the emerging infectious viral agent that had to threaten the world with its epidemic since 2003 with SARS and 2013 with MERS virus. This virus again stuck the whole world with its robust pandemic in 2019whena novel form of the corona virus was emerged in and infect the local population of Wuhan, China. The virus named as SARS CoV-2 and the disease caused by this infectious virus is introduced as COVID 19. Since December 2019, this virus took more than 432, 973 lives all around the world. This study elaborates the role of HIV and HCV drug in targeting nsp12 gene of SARS CoV 2 that is responsible for RNA dependent RNA polymerase activity. The work employed homology modelling, structure validation and molecular docking analysis to evaluate the binding affinity and interaction analysis between NSP12 (RdRp) protein and HIV/HCV drugs. Outcome of the study impacted on Nelfinavir (NFV), Raltegravir (RAL) and Delavirdine (DLV) among Anti-HIV and Paritaprevir (PTV), Beclabuvir (BCV) and Ledipasvir (LDV) among Anti-HCV as the most effective inhibitors of SARS CoV-2 RdRp ternary complexes. The drugs have a strong binding affinity with the residues that are present in the active site of RdRp of the virus and essential for its replication. This study establishes significant information in the direction of therapeutic development as we are dealing with the situation where we urgently required medication or vaccine to combat COVID-19. Therefore, this study provides essential molecular information about the FDA approved antiviral drugs that can be used to treat this disease. Importantly, the listed drugs had never prioritized for their effectiveness against COVID-19. Immuno Deficiency Virus (HIV) drugs, HCV drugs and anti-malarial drugs. 18,19
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