El-Mageed H R Abd, Abdelrheem Doaa A, Ahmed Shimaa A, Rahman Aziz A, Elsayed Khaled N M, Ahmed Sayed A, El-Bassuony Ashraf A, Mohamed Hussein S
Micro-analysis and Environmental Research and Community Services Center, Faculty of Science, Beni-Suef University, Beni-Suef City, Egypt.
Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, 62511 Egypt.
Struct Chem. 2021;32(4):1415-1430. doi: 10.1007/s11224-020-01723-5. Epub 2021 Jan 8.
Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection. Then, the protein stability produced score of less than 0.6 for all residues of all studied receptors. This confirmed that these receptors are extremely stable proteins, so it is very difficult to unstable the stability of these proteins through utilizing individual drugs. Hence, we studied the combination and tricombination therapy between bioactive compounds which have the best binding affinity and some antiviral drugs like chloroquine, hydroxychloroquine, azithromycin, simeprevir, baloxavir, lopinavir, and favipiravir to show the effect of combination and tricombination therapy to disrupt the stability of the three major viral targets that are mentioned previously. Also, ADMET study suggested that most of all studied bioactive compounds are safe and nontoxic compounds. All results confirmed that caulerpin can be utilized as a combination and tricombination therapy along with the studied antiviral drugs for disrupting the stability of the three major viral receptors (6LU7, 6VYB, and 1R42).
The online version contains supplementary material available at 10.1007/s11224-020-01723-5.
最近，严重急性呼吸综合征冠状病毒2（COVID-19）大流行病毒一直在全球传播。到目前为止，尚未发现有经认证的药物能有效抑制该病毒。科学家们正在努力寻找这种致命病毒的新型安全生物活性抑制剂。在本研究中，我们旨在寻找可能抑制三个主要病毒靶点活性的拮抗剂：严重急性呼吸综合征冠状病毒2 3-胰凝乳蛋白酶样蛋白酶（6LU7）、严重急性呼吸综合征冠状病毒2刺突蛋白（6VYB）以及宿主靶点人类血管紧张素转换酶2（ACE2）受体（1R42），该受体是病毒接触的切入点，研究目的是确定针对COVID-19感染的重要候选药物。然后，所有研究受体的所有残基产生的蛋白质稳定性得分均低于0.6。这证实这些受体是极其稳定的蛋白质，因此很难通过使用单一药物来破坏这些蛋白质的稳定性。因此，我们研究了具有最佳结合亲和力的生物活性化合物与一些抗病毒药物（如氯喹、羟氯喹、阿奇霉素、西美瑞韦、巴洛沙韦、洛匹那韦和法匹拉韦）之间的联合和三联疗法，以显示联合和三联疗法对破坏上述三个主要病毒靶点稳定性的效果。此外，药物代谢动力学（ADMET）研究表明，大多数研究的生物活性化合物都是安全无毒的化合物。所有结果均证实，绿刺参碱可与所研究的抗病毒药物联合及三联使用，以破坏三个主要病毒受体（6LU7、6VYB和1R42）的稳定性。
在线版本包含可在10.1007/s11224-020-01723-5获取的补充材料。
