Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotécnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.
Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.
Molecules. 2020 Nov 29;25(23):5615. doi: 10.3390/molecules25235615.
The worldwide health emergency of the SARS-CoV-2 pandemic and the absence of a specific treatment for this new coronavirus have led to the use of computational strategies (drug repositioning) to search for treatments. The aim of this work is to identify FDA (Food and Drug Administration)-approved drugs with the potential for binding to the spike structural glycoprotein at the hinge site, receptor binding motif (RBM), and fusion peptide (FP) using molecular docking simulations. Drugs that bind to amino acids are crucial for conformational changes, receptor recognition, and fusion of the viral membrane with the cell membrane. The results revealed some drugs that bind to hinge site amino acids (varenicline, or steroids such as betamethasone while other drugs bind to crucial amino acids in the RBM (naldemedine, atovaquone, cefotetan) or FP (azilsartan, maraviroc, and difluprednate); saquinavir binds both the RBM and the FP. Therefore, these drugs could inhibit spike glycoprotein and prevent viral entry as possible anti-COVID-19 drugs. Several drugs are in clinical studies; by focusing on other pharmacological agents (candesartan, atovaquone, losartan, maviroc and ritonavir) in this work we propose an additional target: the spike glycoprotein. These results can impact the proposed use of treatments that inhibit the first steps of the virus replication cycle.
由于 2019 年冠状病毒病（COVID-19）大流行这一全球卫生紧急情况，以及缺乏针对这种新型冠状病毒的特定治疗方法，因此人们采用了计算策略（药物重定位）来寻找治疗方法。本工作的目的是使用分子对接模拟来鉴定美国食品和药物管理局（FDA）批准的、有可能与铰链区、受体结合基序（RBM）和融合肽（FP）上的刺突结构糖蛋白结合的药物。与氨基酸结合的药物对于构象变化、受体识别以及病毒膜与细胞膜融合至关重要。结果表明，有一些药物可与铰链区氨基酸结合（伐伦克林，或倍他米松等类固醇），而其他药物可与 RBM 中的关键氨基酸结合（那拉曲坦、阿托伐醌、头孢替坦）或 FP（阿齐沙坦、马拉维若、双氯非那酸）；沙奎那韦结合 RBM 和 FP。因此，这些药物可能会抑制刺突糖蛋白并阻止病毒进入，成为有希望的抗 COVID-19 药物。有几种药物正在进行临床研究；通过在这项工作中关注其他药理制剂（坎地沙坦、阿托伐醌、洛沙坦、马拉维若和利托那韦），我们提出了另一个靶点：刺突糖蛋白。这些结果可能会影响到抑制病毒复制周期初始步骤的治疗方法的应用。
