Chaudhary Meenakshi, Sehgal Deepak
Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, Uttar Pradesh, India.
J Biomol Struct Dyn. 2022;40(22):11560-11570. doi: 10.1080/07391102.2021.1960195. Epub 2021 Aug 6.
Chikungunya Virus (CHIKV) is having a major impact on humans with potentially life-threatening and debilitating arthritis. The lack of a specific antiviral drug against the CHIKV disease has created an alarming situation to identify or develop potent chemical molecules for its remedial measures. Antiviral therapies for viral diseases are generally expensive and have adverse side effects. Plant-based antiviral natural compounds are the most suitable and best alternative of current antiviral drugs because of less toxicity. In the present study, non-structural protein 3 macrodomain (nsP3) of the CHIKV that is essential for virus replication has been selected for anti CHIKV drug target. The compounds were identified using molecular docking, virtual screening and further evaluated by molecular dynamics (MD) simulation studies. The binding mechanism of each compound was analyzed considering the stability and energetic parameter. We have found six plant-based natural antiviral compounds Baicalin, Rutaecarpine, Amentoflavone, Apigetrin, Luteoloside, and Baloxavir as strong inhibitors of nsP3 of CHIKV. ADMET prediction and target analysis of the selected compounds showed drug likeliness of these compounds. MD simulation studies indicated energetically favorable complex formation between nsP3 and the selected antiviral compounds. Furthermore, the structural effects on these substitutions were analyzed using the principles of each trajectory, which validated the interaction studies. Our analysis suggests a very high probability of these compounds to inhibit nsP3 of CHIKV and could be evaluated for Chikungunya fever drug development. Communicated by Ramaswamy H. Sarma.
基孔肯雅病毒（CHIKV）正在对人类产生重大影响，可引发可能危及生命且使人衰弱的关节炎。缺乏针对基孔肯雅病毒病的特效抗病毒药物，这促使人们迫切需要识别或开发有效的化学分子用于补救措施。针对病毒性疾病的抗病毒疗法通常价格昂贵且有不良副作用。基于植物的抗病毒天然化合物因其低毒性，是当前抗病毒药物最合适且最佳的替代品。在本研究中，已选择对病毒复制至关重要的基孔肯雅病毒非结构蛋白3宏结构域（nsP3）作为抗基孔肯雅病毒药物靶点。通过分子对接、虚拟筛选鉴定化合物，并通过分子动力学（MD）模拟研究进一步评估。考虑稳定性和能量参数分析了每种化合物的结合机制。我们发现六种基于植物的天然抗病毒化合物黄芩苷、吴茱萸次碱、穗花杉双黄酮、芹菜素、木犀草苷和巴洛沙韦是基孔肯雅病毒nsP3的强抑制剂。对所选化合物的ADMET预测和靶点分析表明这些化合物具有成药可能性。MD模拟研究表明nsP3与所选抗病毒化合物之间能形成能量有利的复合物。此外，利用每条轨迹的原理分析了这些取代对结构的影响，验证了相互作用研究。我们的分析表明这些化合物极有可能抑制基孔肯雅病毒的nsP3，可用于评估开发治疗基孔肯雅热的药物。由拉马斯瓦米·H·萨尔马传达。
