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Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 6.2 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.bbadis.2020.165878
Ahmad Abu Turab Naqvi 1 , Kisa Fatima 2 , Taj Mohammad 1 , Urooj Fatima 3 , Indrakant K Singh 4 , Archana Singh 5 , Shaikh Muhammad Atif 6 , Gururao Hariprasad 7 , Gulam Mustafa Hasan 8 , Md Imtaiyaz Hassan 1
Affiliation  

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.



中文翻译:

对SARS-CoV-2基因组,结构,进化,发病机制和治疗方法的见解:结构基因组学方法。

由新型严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的严重呼吸系统疾病的突然出现,最近已成为公共卫生突发事件。SARS-CoV-2的基因组序列分析表明,它与早期报道的SARS-CoV和中东呼吸综合征冠状病毒(MERS-CoV)非常相似。但是,针对SARS-CoV和MERS-CoV的药物的初始测试对控制SARS-CoV-2无效。本研究突出了SARS-CoV-2感染的基因组学,蛋白质组学,发病机理和治疗策略。我们对SARS-CoV-2中潜在的药物靶蛋白进行了序列分析,并将其与SARS-CoV和MERS病毒进行了比较。还对SARS-CoV-2编码区和非编码区的突变,遗传多样性和致病性进行了分析。已对药物靶蛋白进行了详细的结构分析,以深入了解发病机理,结构功能关系以及结构指导的治疗方法的发展。在SARS-CoV-2感染的情况下,细胞因子谱和炎性信号传导是不同的。我们还重点介绍了可能的疗法及其作用机制,以及随后的临床表现。我们的分析表明,SARS-CoV-2基因组序列的最小变化可能与靶蛋白结构的急剧变化有关,这使可用药物无效。在SARS-CoV-2感染的情况下,细胞因子谱和炎性信号传导是不同的。我们还重点介绍了可能的疗法及其作用机制,以及随后的临床表现。我们的分析表明,SARS-CoV-2基因组序列的最小变化可能与靶蛋白结构的急剧变化有关,这使可用药物无效。在SARS-CoV-2感染的情况下,细胞因子谱和炎性信号传导是不同的。我们还重点介绍了可能的疗法及其作用机制,以及随后的临床表现。我们的分析表明,SARS-CoV-2基因组序列的最小变化可能与靶蛋白结构的急剧变化有关,这使可用药物无效。

更新日期:2020-06-13
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