Tariq Asma, Mateen Rana Muhammad, Afzal Muhammad Sohail, Saleem Mahjabeen
Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.
Department of Life Sciences, School of Science, University of Management and Technology, Lahore, Pakistan.
Int J Infect Dis. 2020 Sep;98:166-175. doi: 10.1016/j.ijid.2020.06.063. Epub 2020 Jun 21.
With the increasing number of people suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for the current situation.
In a quest to find a potential drug against this virus, 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs were investigated for activity against both the protease and spike proteins of SARS-CoV-2 using an in silico approach. Molecular docking analysis followed by molecular dynamics simulation was performed to estimate the binding and stability of the complexes.
This study identified a single drug - paromomycin - with activity against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity for both targets of coronavirus. The results also showed that no antimalarial drug exhibited effective binding for either S1 or protease.
This study found that paromomycin may be an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion, but also to the spike domain, with high stability. Furthermore, none of the antimalarial drugs showed strong binding affinity for either protease or the receptor binding domain (RBD).
随着感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）所致2019冠状病毒病（COVID-19）的人数不断增加，迫切需要寻找针对这一流行病的有效治疗方法。药物重新利用似乎是解决当前情况的办法。
为了寻找一种针对这种病毒的潜在药物，采用计算机模拟方法，对15种抗疟药物（包括氯喹）和2413种美国食品药品监督管理局批准的药物进行了针对SARS-CoV-2蛋白酶和刺突蛋白活性的研究。进行了分子对接分析，随后进行分子动力学模拟，以评估复合物的结合和稳定性。
本研究确定了一种单一药物——巴龙霉素——对SARS-CoV-2的两个靶点即刺突蛋白（S1）和蛋白酶结构域具有活性。发现巴龙霉素对冠状病毒的两个靶点都有很强的结合亲和力。结果还表明，没有一种抗疟药物对S1或蛋白酶表现出有效结合。
本研究发现，巴龙霉素可能是一种针对冠状病毒的有效双靶点药物，因为它不仅与病毒粒子的蛋白酶结构域结合，还与刺突结构域结合，且稳定性高。此外，没有一种抗疟药物对蛋白酶或受体结合结构域（RBD）表现出强结合亲和力。
