INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi 110007, India.
Maharshi Dayanand University, Rohtak, Haryana 124001, India.
Genomics. 2022 Sep;114(5):110466. doi: 10.1016/j.ygeno.2022.110466. Epub 2022 Aug 27.
The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis of in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with the VOCs - Delta and Omicron, within Recovered and Mortality patients. Statistical analysis highlighted significant mutations - T4685A, N4992N, and G5063S in RdRp; T19R in NTD spike; K444N and N532H in RBD spike, associated with Delta mortality. Mutations, T19I in NTD spike, Q493R and N440K in the RBD spike were significantly associated with Omicron mortality. We performed molecular docking for possible effect of significant mutations on the binding of Remdesivir. We found that Remdesivir showed less binding efficacy with the mutant Spike protein of both Delta and Omicron mortality compared to recovered patients. This indicates that mortality associated mutations could have a modulatory effect on drug binding which could be associated with disease outcome.
由于新出现的严重急性呼吸系统综合征冠状病毒 2 (SARS-CoV-2) 变异株，全球 COVID-19 大流行仍在继续。在这里，我们对感染了 Delta 和奥密克戎变异株的患者体内 SARS-CoV-2 基因组突变的动态进行了综合分析，这些患者包括康复者和死亡者。统计分析突出了 RdRp 中显著的突变 - T4685A、N4992N 和 G5063S；NTD 刺突中的 T19R；RBD 刺突中的 K444N 和 N532H，这些突变与 Delta 死亡率相关。突变，NTD 刺突中的 T19I，RBD 刺突中的 Q493R 和 N440K 与奥密克戎死亡率显著相关。我们对可能对雷迪昔韦结合产生影响的显著突变进行了分子对接。我们发现，雷迪昔韦与 Delta 和奥密克戎死亡率患者的突变 Spike 蛋白的结合效果较差，而与康复者相比。这表明与死亡率相关的突变可能对药物结合具有调节作用，这可能与疾病结果有关。
