骆驼乳蛋白中新型基孔肯雅病毒非结构蛋白 4 抑制肽的鉴定与分子对接
Identification and molecular docking of novel chikungunya virus NSP4 inhibitory peptides from camel milk proteins.
机构信息
Molecular Biology Department, Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia.
Department of Biochemistry, Faculty of Sciences, King Abdulaziz University Jeddah, Saudi Arabia.
出版信息
J Biomol Struct Dyn. 2024;42(19):9961-9976. doi: 10.1080/07391102.2023.2254398. Epub 2023 Sep 5.
The chikungunya (CHIK) virus is an arbovirus belonging to the alphavirus ( family). Around 85% of infected individuals suffer from symptoms such as high fever and severe joint pain; about 30 to 40% will develop a chronic joint illness. The Nsp4 protease is the most conserved protein in the alphavirus family and serves as an RNA-dependent RNA polymerase (RdRp). Targeting this enzyme might inhibit the CHIKV replication cycle. This work aims to study the CHIKV RdRp inhibitory effect of peptides derived from camel milk protein as antiviral peptides. Various bioinformatics tools were recruited to identify, screen, predict and assess peptides obtained from camel milk as antiviral peptides (AVPs). During this study, CHIKV Nsp4 (polymerase) was used as a target to be inhibited by interaction with peptides derived from camel milk protein. Among 91 putative bioactive peptides, the best predicted 5 were further evaluated. Molecular docking showed that the top 5 AVPs generated better docking scores and interacted well with active sites of Nsp4 by the formation of different hydrogen bonds as well as other bonds. AVP63 and AVP20 showed the best Molecular docking and MD simulation results. The residue 315ASP of the GDD motif (catalytic core) exhibited a favorable interaction with the AVPs. The findings of this study suggest that the AVP20 derived from camel milk protein can be a potential novel CHIKV polymerase inhibitor.Communicated by Ramaswamy H. Sarma.
基孔肯雅热(CHIK)病毒是一种属于甲病毒(家族)的虫媒病毒。大约 85%的感染个体患有高热和严重关节疼痛等症状;约 30%至 40%将发展为慢性关节疾病。Nsp4 蛋白酶是甲病毒家族中最保守的蛋白质,作为 RNA 依赖性 RNA 聚合酶(RdRp)。靶向这种酶可能会抑制 CHIKV 复制周期。这项工作旨在研究源自骆驼乳蛋白的肽作为抗病毒肽对 CHIKV RdRp 的抑制作用。各种生物信息学工具被招募来识别、筛选、预测和评估源自骆驼乳的肽作为抗病毒肽(AVP)。在这项研究中,CHIKV Nsp4(聚合酶)被用作通过与源自骆驼乳蛋白的肽相互作用来抑制的靶标。在 91 个假定的生物活性肽中,进一步评估了最佳预测的 5 个。分子对接表明,前 5 个 AVP 产生了更好的对接分数,并通过形成不同氢键以及其他键与 Nsp4 的活性位点很好地相互作用。AVP63 和 AVP20 显示出最佳的分子对接和 MD 模拟结果。GDD 基序(催化核心)的残基 315ASP 与 AVP 表现出有利的相互作用。这项研究的结果表明,源自骆驼乳蛋白的 AVP20 可以成为一种有潜力的新型 CHIKV 聚合酶抑制剂。由 Ramaswamy H. Sarma 传达。