Vishvakarma Vijay Kumar, Pal Shweta, Singh Prashant, Bahadur Indra
Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi, India.
Chemistry Department, Faculty of Natural and Agricultural Sciences, North-West University, Mmabatho 2735, South Africa.
J Mol Struct. 2022 Mar 5;1251:131965. doi: 10.1016/j.molstruc.2021.131965. Epub 2021 Nov 20.
SARS-CoV-2 is drastically spread across the globe in a short period of time and affects the lives of billions. There is a need to find the promising drugs like candidates against the inhibition of novel corona virus or SARS-CoV-2. Herein, the interaction on sex hormones (testosterone and progesterone) with Mpro of SARS-CoV-2 was investigated with the help of molecular docking. The binding energy for the formation complex between the progesterone and testosterone with main protease of SARS-CoV-2 are -86.05 and -91.84 kcal/mol, respectively. From this, it can be understood that testosterone showed better binding affinity with Mpro of nCoV and thus, more inhibition of the main protease. Then, the binding was further studied using molecular dynamics simulations at different temperatures (300, 310 and 325) K. It has been observed that the formations of complex between the Mpro of nCoV with testosterone/ progesterone is better at 300 K than 310 and 325 K. Further, it is found that the more effective binding of testosterone with Mpro of nCoV is observed than the progesterone based on the RMSD, RMSF and H-bond trajectories. Results indicate the promising nature of testosterone towards the inhibition of Mpro of nCoV.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在短时间内迅速在全球传播，影响了数十亿人的生活。需要找到有前景的药物，如针对新型冠状病毒或SARS-CoV-2抑制作用的候选药物。在此，借助分子对接研究了性激素（睾酮和孕酮）与SARS-CoV-2主蛋白酶（Mpro）之间的相互作用。孕酮和睾酮与SARS-CoV-2主蛋白酶形成复合物的结合能分别为-86.05和-91.84千卡/摩尔。由此可以理解，睾酮与新型冠状病毒的Mpro表现出更好的结合亲和力，因此对主蛋白酶的抑制作用更强。然后，在不同温度（300、310和325）K下使用分子动力学模拟进一步研究这种结合。据观察，新型冠状病毒的Mpro与睾酮/孕酮之间形成的复合物在300 K时比在310 K和325 K时更好。此外，基于均方根偏差（RMSD）、均方根波动（RMSF）和氢键轨迹发现，睾酮与新型冠状病毒的Mpro的结合比孕酮更有效。结果表明睾酮对抑制新型冠状病毒的Mpro具有潜在的应用前景。
