Fatoki Toluwase Hezekiah
Applied Bioinformatics Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Oye, Nigeria.
Front Bioinform. 2023 Jun 7;3:1123307. doi: 10.3389/fbinf.2023.1123307. eCollection 2023.
Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are -5.8 and -5.4 kcal mol respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase.
人腺病毒（HAdVs）是无包膜的小型双链DNA（dsDNA）病毒，可引起无症状感染、临床综合征，并使免疫功能低下者极易感染。本研究的目的是确定关键的宿主蛋白和HAdV假定蛋白，这些蛋白可被开发为抗HAdV治疗的潜在宿主-病毒靶点。在此，基于与人类免疫缺陷病毒（HIV）抗逆转录病毒药物治疗靶点的系统发育关系，对选定的HAdV假定蛋白的功能进行了计算预测，并对HAdV DNA聚合酶的分子动力学和结合亲和力进行了表征。本研究使用了38种人腺病毒（HAdV）的假定蛋白（HPs）。结果表明，HAdV DNA聚合酶（P03261）与人类端粒酶逆转录酶（O14746）和HLA-B（P0188９）基因相关。抗逆转录病毒药物（ARVDs）的五个分子靶点（嘌呤核苷磷酸化酶、端粒酶逆转录酶、趋化因子受体5、HLA-B和核受体亚家族1I组成员2）在抗HIV感染机制中与CD4、芳烃受体、FK506结合蛋白4、糖皮质激素受体、热休克蛋白90α家族成员1和STUB1蛋白具有良好的协同作用/网络关系。结果表明，阿巴卡韦和齐多夫定与HAdV DNA聚合酶结合的自由能分数分别为-5.8和-5.4千卡/摩尔。此外，与阿巴卡韦和齐多夫定相比，对照药物西多福韦和更昔洛韦对HAdV DNA聚合酶的结合亲和力较低。观察到阿巴卡韦和齐多夫定与HAdV DNA聚合酶（ASP742、ALA743、LEU772、ARG773和VAL776）的结合具有相似性。总之，预测阿巴卡韦和齐多夫定联合使用可能是针对HAdV DNA聚合酶控制HAdV感染的潜在疗法。
