Investigation of the interactions of HSA and SARS-CoV-2 papain-like protease against eugenol for novel COVID-19 drug discovery: spectroscopic and insilico study

Coronavirus family consist of a member known as SARS-CoV-2, spread drastically in 2019 (Covid-19), affecting millions of people worldwide. Till date there is no clear-clinical therapy or drug, targeted to cure this serious disease. Researches are going on to prevent this corona virus. Here, we tried to explore a novel SARS-CoV-2 papain-like protease as a potential inhibitor. Finally, eugenol was docked with this protease to find prime SARS-inhibitors. <i>In silico</i> studies revealed that eugenol binds to the active site of SARS-CoV-2 papain-like protease with appropriate binding. Moreover, the MD simulation for 100 ns and MMPBSA calculation reveals that eugenol possess potential phytotherapeutic properties against COVID-19. The interaction of eugenol with human serum albumin has been examined by using fluorescence, UV–vis spectroscopy, circular dichroism as well as computational techniques such as molecular docking, molecular dynamic simulation and MMPBSA calculation. Overall investigation shows eugenol having good affinity for HSA <i>K</i>_a 6.80 × 10⁶ M⁻¹. Communicated by Ramaswamy H. Sarma

冠状病毒科包含严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）这一成员，该病毒于2019年暴发式传播，引发新型冠状病毒肺炎（COVID-19），已在全球范围内影响数百万民众。截至目前，尚无针对该重症疾病的明确临床治疗方案或靶向治愈药物。目前相关研究正持续推进，以防控该冠状病毒。本研究以新型SARS-CoV-2木瓜样蛋白酶为潜在靶点，筛选抗该病毒的抑制剂。最终，我们将丁香酚与该蛋白酶进行分子对接（Molecular Docking），以筛选出最优的抗SARS病毒抑制剂。计算机模拟（In silico）研究结果显示，丁香酚可与SARS-CoV-2木瓜样蛋白酶的活性位点特异性结合，结合状态良好。此外，通过100纳秒的分子动力学（Molecular Dynamics, MD）模拟与分子力学-泊松玻尔兹曼表面积（Molecular Mechanics-Poisson Boltzmann Surface Area, MMPBSA）计算，证实丁香酚具备对抗COVID-19的潜在植物源治疗活性。本研究还通过荧光光谱、紫外-可见分光光度法、圆二色谱（Circular Dichroism, CD）等实验手段，结合分子对接、分子动力学模拟及MMPBSA计算等计算机技术，对丁香酚与人血清白蛋白（Human Serum Albumin, HSA）的相互作用进行了系统研究。整体研究结果表明，丁香酚与HSA具有良好的结合亲和力，其结合常数Ka为6.80×10⁶ M⁻¹。本文由Ramaswamy H. Sarma转交刊发。