In this paper, we studied the in silico interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. Caffeine and nicotine are interesting structures for interactions because of their similar structure to the candidate antiviral drugs. Our results reveal that caffeine or nicotine in a specific molar ratio to 6LZG shows a very strong interaction and indicate that caffeine is more efficient in the interaction with 6LZG and further blocking of this site against S protein binding. Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2.

中文翻译：

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通过阻断SARS-CoV-2和ACE2受体的S蛋白抑制烟碱/咖啡因作用的计算机研究

在本文中，我们研究了计算机通过分子动力学（MD）模拟，血管紧张素转化酶2（ACE2）人类受体与两种生物活性化合物，即尼古丁和咖啡因的相互作用。模拟显示，咖啡因和尼古丁可有效阻断ACE2暴露于严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）的突波（S）蛋白中。我们选择了ACE2-S蛋白的两个最重要的活性位点，即6LZG和6VW1，它们在S蛋白与受体的相互作用中起着至关重要的作用，因此，我们通过MD模拟研究了它们与尼古丁和咖啡因的相互作用。咖啡因和尼古丁是相互作用的有趣结构，因为它们与候选抗病毒药物的结构相似。我们的结果表明，咖啡因或尼古丁与6LZG的摩尔比特定，显示出非常强的相互作用，并表明咖啡因在与6LZG相互作用以及进一步阻止该位点与S蛋白结合方面更有效。此外，我们研究了将ACE2受体S蛋白与烟碱或咖啡因与候选或获批准的SARS-CoV-2治疗抗病毒药混合使用时的相互作用。我们的医学博士模拟表明，咖啡因与利巴韦林的组合显示出与6VW1的较强相互作用，而在使用favipiravir +尼古丁的情况下，6LZG显示出这些相互作用的有效功效，这表明这些组合有效阻断ACE2受体抵抗SARS-CoV- 2。