Kulkarni Seema A, Krishnan Sabari B B, Chandrasekhar Bavya, Banerjee Kaushani, Sohn Honglae, Madhavan Thirumurthy
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Chengalpattu, India.
Computational Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Chengalpattu, India.
Front Chem. 2021 Sep 27;9:735768. doi: 10.3389/fchem.2021.735768. eCollection 2021.
disease-2019 (COVID-19) has caused a severe impact on almost all aspects of human life and economic development. Numerous studies are being conducted to find novel therapeutic strategies to overcome COVID-19 pandemic in a much effective way. L. (), a marine microalga, known for its antiviral property, was considered for this study to determine the antiviral efficacy against severe acute respiratory syndrome-associated -2 (). The algal sample was dried and subjected to ethanolic extraction, followed by purification and analysis using gas chromatography-coupled mass spectrometry (GC-MS). Forty-three known compounds were identified and docked against the S receptor binding domain (RBD) of the spike (S) glycoprotein. The compounds that exhibited high binding affinity to the RBD of S protein were further analyzed for their chemical behaviour using conceptual density-functional theory (C-DFT). Finally, pharmacokinetic properties and drug-likeliness studies were carried out to test if the compounds qualified as potential leads. The results indicated that mainly phenols, polyenes, phytosteroids, and aliphatic compounds from the extract, such as 2,4-di-tert-butylphenol (2,4-DtBP), doconexent, 4,8,13-duvatriene-1,3-diol (DTD), retinoyl-β-glucuronide 6',3'-lactone (RBGUL), and retinal, showed better binding affinity to the target. Pharmacokinetic validation narrowed the list to 2,4-DtBP, retinal and RBGUL as the possible antiviral candidates that could inhibit the viral spike protein effectively.
2019年冠状病毒病（COVID-19）对人类生活和经济发展的几乎所有方面都造成了严重影响。目前正在进行大量研究，以寻找新颖的治疗策略，更有效地克服COVID-19大流行。本研究考虑使用以其抗病毒特性而闻名的海洋微藻L.（）来确定其对严重急性呼吸综合征相关冠状病毒2（）的抗病毒功效。将藻类样品干燥并进行乙醇提取，然后使用气相色谱-质谱联用（GC-MS）进行纯化和分析。鉴定出43种已知化合物，并将其与刺突（S）糖蛋白的S受体结合域（RBD）进行对接。使用概念密度泛函理论（C-DFT）进一步分析对S蛋白的RBD表现出高结合亲和力的化合物的化学行为。最后，进行药代动力学性质和类药性质研究，以测试这些化合物是否符合潜在先导物的条件。结果表明，提取物中的主要酚类、多烯类、植物甾醇类和脂肪族化合物，如2,4-二叔丁基苯酚（2,4-DtBP）、二十二碳六烯酸、4,8,13-杜瓦三烯-1,3-二醇（DTD）、视黄酰-β-葡萄糖醛酸6',3'-内酯（RBGUL）和视黄醛，对靶点表现出更好的结合亲和力。药代动力学验证将名单缩小到2,4-DtBP、视黄醛和RBGUL，它们可能是能够有效抑制病毒刺突蛋白的抗病毒候选物。
