Saraswat Juhi, Riaz Ufana, Patel Rajan
Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India.
J Mol Liq. 2022 Aug 1;359:119277. doi: 10.1016/j.molliq.2022.119277. Epub 2022 May 3.
The pandemic due to COVID-19 caused by SARS-CoV-2 has led to the recorded deaths worldwide and is still a matter of concern for scientists to find an effective counteragent. The combination therapy is always been a successful attempt in treating various threatful diseases. Recently, Ionic liquids (ILs) are known for their antiviral activity. Fascinating tunable properties of ILs make them a potential candidate for designing the therapeutic agent. The concern while using ILs in biomedical field remains is toxicity therefore, choline-based ILs were used in the study as they are considered to be greener as compared to other ILs. In the present study strategically, we performed the blind molecular docking of antiviral drug (Abacavir, Acyclovir, and Galidesivir)-choline based ILs conjugates with the target protein (M protease). The molecules were screened on the basis of binding energy. The data suggested that the combination of AVDs-ILs have greater antiviral potential as compared to the drugs and ILs alone. Further, the ADME properties and toxicity analysis of the screened conjugates was done which revealed the non-toxicity of the conjugates. Additionally, the energetic profiling of the ILs drugs and their conjugates was done using DFT calculations which revealed the stability of the conjugates and have a better option to be developed as a therapeutic agent. Also, from molecular dynamic simulation was done and results showed the stability of the complex formed between target protein and the designed conjugates of AVDs and ILs.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病大流行已导致全球有记录的死亡，寻找有效的对抗剂仍是科学家们关注的问题。联合疗法一直是治疗各种威胁性疾病的成功尝试。最近，离子液体（ILs）因其抗病毒活性而闻名。离子液体迷人的可调谐特性使其成为设计治疗剂的潜在候选者。在生物医学领域使用离子液体时，人们关注的仍然是毒性，因此，在该研究中使用了基于胆碱的离子液体，因为与其他离子液体相比，它们被认为更环保。在本研究中，我们策略性地对抗病毒药物（阿巴卡韦、阿昔洛韦和加利地韦）与基于胆碱的离子液体的共轭物与目标蛋白（M蛋白酶）进行了盲分子对接。根据结合能对分子进行筛选。数据表明，与单独的药物和离子液体相比，抗病毒药物-离子液体的组合具有更大的抗病毒潜力。此外，对筛选出的共轭物进行了药物代谢动力学性质和毒性分析，结果表明共轭物无毒。此外，使用密度泛函理论计算对离子液体药物及其共轭物进行了能量分析，结果表明共轭物具有稳定性，是开发治疗剂的更好选择。同时，进行了分子动力学模拟，结果表明目标蛋白与设计的抗病毒药物和离子液体的共轭物之间形成的复合物具有稳定性。
