Bhati Shipra, Kaushik Vikas, Singh Joginder
Department of Chemistry, The Oxford College of Engineering, Bommanhalli, Bangalore-560068, Karnataka, India.
Department of Biotechnology, Lovely Professional University, Phagwara-144411, Punjab, India.
J Mol Struct. 2021 Aug 5;1237:130380. doi: 10.1016/j.molstruc.2021.130380. Epub 2021 Apr 7.
The current outbreak of Coronavirus Disease 2019 (COVID-19) pandemic has reported thousands of deaths worldwide due to the rapid transmission rate and the lack of antiviral drugs and vaccinations. There is an urgent need to develop potential antiviral drug candidates for the prevention of COVID-19 infection. In the present study, a series of potential inhibitors targeting SARS-CoV 3CL protease were rationally designed by incorporating gamma lactam ring, and various fluoro substituted heterocyclic ring systems to the flavonoid scaffold. The prediction of drug-likeness, oral bioavailability, toxicity, synthetic accessibility, and ADMET properties was made by computational means. Quercetin was used as standard. The binding affinity of the ligands towards the 3CL protease target was examined using docking simulations. The designed ligands possess favourable pharmacokinetic and pharmacodynamic properties. Ligand L4, L8, and L14 appeared to be the lead compounds in the series and can be considered for further and validation.
2019年冠状病毒病（COVID-19）大流行目前在全球已造成数千人死亡，原因是其传播速度快，且缺乏抗病毒药物和疫苗。迫切需要开发潜在的抗病毒候选药物以预防COVID-19感染。在本研究中，通过将γ-内酰胺环以及各种氟取代的杂环系统引入类黄酮骨架，合理设计了一系列靶向严重急性呼吸综合征冠状病毒（SARS-CoV）3C样蛋白酶的潜在抑制剂。通过计算手段对药物相似性、口服生物利用度、毒性、合成可及性和药物代谢及毒性性质（ADMET）进行了预测。以槲皮素作为标准。使用对接模拟检查配体与3C样蛋白酶靶点的结合亲和力。所设计的配体具有良好的药代动力学和药效学性质。配体L4、L8和L14似乎是该系列中的先导化合物，可考虑用于进一步研究和验证。
