Anti-HIV drug repurposing against SARS-CoV-2.
Anti-HIV drug repurposing against SARS-CoV-2.
复制标题
抗 HIV 药物重新用于对抗 SARS-CoV-2
作者：
2019年12月，一种新型严重急性呼吸综合征人类冠状病毒（SARS HCoV）从呼吸道疾病患者中被发现（ICTV命名为SARS-CoV-2），最近已成为对世界公共卫生的严重威胁。然而，目前还没有发现有效抑制该病毒的批准药物。由于已有报道HIV蛋白酶抑制剂可以通过靶向SARS-CoV-1 3CLpro作为抗SARS药物，因此我们选择了六种已批准的抗HIV药物，并研究了它们与3CLpro的结合相互作用，以评估它们成为由SARS-CoV-2感染引起的新型冠状病毒肺炎（COVID-19）临床药物的潜力。分子对接结果表明，SARS-CoV-2的3CLpro与所有抑制剂的结合亲和力均高于SARS-CoV-1。两个对接得分高的对接复合物（茚地那韦和地瑞那韦）进一步进行MM-PBSA结合自由能计算，以详细说明这两种蛋白酶抑制剂与SARS HCoV 3CLpro之间的分子相互作用。我们的研究结果显示，在测试的抑制剂中，达芦那韦与SARS-CoV-2和SARS-CoV-1 3CLpro的结合亲和力最高，表明其可能具有作为抗COVID-19临床药物的潜力。通过分子动力学模拟研究了HIV蛋白酶抑制剂与SARS-CoV-2 3CLpro（与SARS-CoV-1相比）结合亲和力增加的机制。我们的研究提供了对SARS HCoV 3CLpro和抑制剂之间相互作用过程中结构灵活性的可能作用的深入了解，并揭示了基于结构的抗COVID-19药物设计靶向SARS-CoV-2 3CLpro。2019年12月，一种新型严重急性呼吸综合征人类冠状病毒（SARS HCoV）从呼吸道疾病患者中被发现（ICTV命名为SARS-CoV-2），最近已成为对世界公共卫生的严重威胁。
A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health. However, no approved drugs have been found to effectively inhibit the virus. Since it has been reported that HIV protease inhibitors can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose six approved anti-HIV drugs and investigated their binding interactions with 3CLpro to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection. The molecular docking results indicate that the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than does SARS-CoV-1. Two docking complexes (indinavir and darunavir) with high docking scores were further subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two protease inhibitors and SARS HCoV 3CLpro. Our results show that, among the inhibitors tested, darunavir has the highest binding affinity with SARS-CoV-2 and SARS-CoV-1 3CLpro, indicating that it may have the potential to be used as an anti-COVID-19 clinical drug. The mechanism behind the increased binding affinity of HIV protease inhibitors toward SARS-CoV-2 3CLpro (as compared to SARS-CoV-1) was investigated by MD simulations. Our study provides insight into the possible role of structural flexibility during interactions between SARS HCoV 3CLpro and inhibitors and sheds light on structure-based design of anti-COVID-19 drugs targeting SARS-CoV-2 3CLpro. A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
3
作者：
Vanommeslaeghe, K.;Hatcher, E.;Acharya, C.;Kundu, S.;Zhong, S.;Shim, J.;Darian, E.;Guvench, O.;Lopes, P.;Vorobyov, I.;MacKerell, A. D., Jr.
通讯作者：
MacKerell, A. D., Jr.
SNP 衍生的人类 P5CR 突变体的计算机筛选、分子对接和分子动力学研究
DOI：
10.1080/07391102.2016.1222967
发表时间：
2017-01-01
影响因子：
4.4
作者：
Sang, Peng;Hu, Wei;Meng, Zhao-Hui
通讯作者：
Meng, Zhao-Hui
乙氧基磺隆衍生物作为靶向乙酰羟酸合酶的新型抗真菌剂的化学制备、生物学评价和3D-QSAR
影响因子：
6.7
作者：
Wu, Ren-Jun;Ren, Tongtong;Wang, Jian-Guo
通讯作者：
Wang, Jian-Guo
DOI：
10.1016/j.bbrc.2004.04.083
发表时间：
2004-06-04
影响因子：
3.1
作者：
Yamamoto N;Yang R;Yoshinaka Y;Amari S;Nakano T;Cinatl J;Rabenau H;Doerr HW;Hunsmann G;Otaka A;Tamamura H;Fujii N;Yamamoto N
通讯作者：
Yamamoto N