Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.
Department of Clinical Research and Leadership, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States of America.
PLoS One. 2022 May 31;17(5):e0268909. doi: 10.1371/journal.pone.0268909. eCollection 2022.
COVID-19 outbreak associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) raised health concerns across the globe and has been considered highly transmissible between people. In attempts for finding therapeutic treatment for the new disease, this work has focused on examining the polymerase inhibitors against the SARS-CoV-2 nsp12 and co-factors nsp8 and nsp7. Several polymerase inhibitors were examined against PDB ID: 6M71 using computational analysis evaluating the ligand's binding affinity to replicating groove to the active site. The findings of this analysis showed Cytarabine of -5.65 Kcal/mol with the highest binding probability (70%) to replicating groove of 6M71. The complex stability was then examined over 19 ns molecular dynamics simulation suggesting that Cytarabine might be possible potent inhibitor for the SARS-CoV-2 RNA Dependent RNA Polymerase.
COVID-19 疫情爆发与严重急性呼吸系统综合症冠状病毒(SARS-CoV-2)有关,引起了全球的健康关注,并且被认为在人与人之间具有高度传染性。在寻找新疾病治疗方法的尝试中,这项工作集中研究了针对 SARS-CoV-2 nsp12 和辅助因子 nsp8 和 nsp7 的聚合酶抑制剂。使用计算分析评估配体与复制沟的结合亲和力对活性位点,对几种聚合酶抑制剂进行了针对 PDB ID:6M71 的检查。该分析的结果显示,阿糖胞苷的结合亲和力为-5.65 Kcal/mol,与 6M71 的复制沟的结合概率最高(70%)。然后通过 19 纳秒的分子动力学模拟检查了复合物的稳定性,表明阿糖胞苷可能是 SARS-CoV-2 RNA 依赖性 RNA 聚合酶的潜在有效抑制剂。