Erukainure Ochuko L, Muhammad Aliyu, Ravichandran Rahul, Abarshi Musa M, Katsayal Sanusi B, Abubakar Murtala B, Abiodun Ya'qub U, Atolani Olubunmi, Preissner Robert, Banerjee Priyanka
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa.
Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria.
Toxicol Rep. 2024 Nov 22;13:101825. doi: 10.1016/j.toxrep.2024.101825. eCollection 2024 Dec.
The multiple mutation of the spike (S) protein of the Omicron SARS-CoV-2 variant is a major concern, as it has been implicated in the severity of COVID-19 and its complications. These mutations have been attributed to COVID-19-infected immune-compromised individuals, with HIV patients being suspected to top the list. The present study investigated the mutation of the S protein of the omicron variant in comparison to the Delta and Wuhan variants. It also investigated the molecular interactions of antiretroviral drugs (ARVd) vis-à-vis dolutegravir, lamivudine, tenofovir-disoproxilfumarate and lenacapavir with the initiation and termination codons of the mRNAs of the mutated proteins of the omicron variant using computational tools. The complete genome sequences of the respective S proteins for omicron (OM066778.1), Delta (OK091006.1) and Wuhan (NC 045512.2) SARS-CoV-2 variants were retrieved from the National Center for Biotechnology Information (NCBI) database. Evolutionary analysis revealed high trends of mutations in the S protein of the omicron SARS-CoV-2 variant compared to the delta and Wuhan variants coupled with 68 % homology. The sequences of the translation initiation sites (TISs), translation termination sites (TTSs), high mutation region-1 (HMR1) and high region mutation-2 (HMR2) mRNAs were retrieved from the full genome of the omicron variant S protein. Molecular docking analysis revealed strong molecular interactions of ARVd with TISs, TTSs, HMR1 and HMR2 of the S protein mRNA. These results indicate mutations in the S protein of the Omicron SARS-CoV-2 variant compared to the Delta and Wuhan variants. These mutation points may present new therapeutic targets for COVID-19.
奥密克戎 SARS-CoV-2 变体刺突（S）蛋白的多重突变是一个主要问题，因为它与 COVID-19 的严重程度及其并发症有关。这些突变归因于感染 COVID-19 的免疫功能低下个体，其中 HIV 患者被怀疑位居榜首。本研究调查了奥密克戎变体 S 蛋白与德尔塔和武汉变体相比的突变情况。它还使用计算工具研究了抗逆转录病毒药物（ARVd）与多替拉韦、拉米夫定、替诺福韦酯富马酸盐和伦卡帕韦相对于奥密克戎变体突变蛋白 mRNA 的起始和终止密码子的分子相互作用。从国家生物技术信息中心（NCBI）数据库中检索了奥密克戎（OM066778.1）、德尔塔（OK091006.1）和武汉（NC 045512.2）SARS-CoV-2 变体各自 S 蛋白的完整基因组序列。进化分析显示，与德尔塔和武汉变体相比，奥密克戎 SARS-CoV-2 变体的 S 蛋白中存在高突变趋势，且同源性为 68%。从奥密克戎变体 S 蛋白的全基因组中检索了翻译起始位点（TIS）、翻译终止位点（TTS）、高突变区域-1（HMR1）和高区域突变-2（HMR2）mRNA 的序列。分子对接分析显示 ARVd 与 S 蛋白 mRNA 的 TIS、TTS、HMR1 和 HMR2 有强烈的分子相互作用。这些结果表明，与德尔塔和武汉变体相比，奥密克戎 SARS-CoV-2 变体的 S 蛋白存在突变。这些突变点可能为 COVID-19 提供新的治疗靶点。
