Department of Physical Sciences, Indian Institute of Science Education and Research, Mohali, India.
Graduate School of Systemic Neuroscience, Ludwig Maximilian University of Munich, Munich, Germany.
PLoS One. 2021 Mar 18;16(3):e0248553. doi: 10.1371/journal.pone.0248553. eCollection 2021.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. One of the major concerns involving the SARS-COV-2 is the mutation rate, which enhances the virus evolution and genome variability, thereby making the design of therapeutics difficult. In this study, we identified the most common haplotypes from the haplotype network. The conserved genes and population level variants were analysed. Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3) and 3-Chymotrypsin like protease (3CLpro or NSP5), which were conserved at the highest threshold, were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs, which are suggested for further pre-clinical and clinical trials. This particular study provides a comprehensive targeting of the conserved genes. We also identified the mutation frequencies across the viral genome.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是一种新型人类冠状病毒(HCoV),最初于 2019 年 12 月在中国武汉市报告。这种急性感染引起了类似肺炎的症状和其他呼吸道疾病。其较高的传播和感染率使其能够在短时间内迅速在全球范围内传播。涉及 SARS-COV-2 的主要问题之一是突变率,这增强了病毒的进化和基因组变异性,从而使治疗药物的设计变得困难。在这项研究中,我们从单倍型网络中确定了最常见的单倍型。分析了保守基因和群体水平变异。非结构蛋白 10(NSP10)、核蛋白、木瓜蛋白酶样蛋白酶(Plpro 或 NSP3)和 3-糜蛋白酶样蛋白酶(3CLpro 或 NSP5)的保守性最高,被用作分子动力学模拟的药物靶点。达非那新、比索洛尔、比克替拉韦、阿利维仑和厄贝沙坦是潜在的药物,建议进一步进行临床前和临床试验。这项特别的研究提供了对保守基因的全面靶向。我们还确定了病毒基因组中突变的频率。