Promising Experimental Anti-SARS-CoV-2 Agent "SLL-0197800": The Prospective Universal Inhibitory Properties against the Coming Versions of the Coronavirus.
Promising Experimental Anti-SARS-CoV-2 Agent "SLL-0197800": The Prospective Universal Inhibitory Properties against the Coming Versions of the Coronavirus.
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有希望的实验性抗SARS-COV-2代理“ SLL-0197800”：针对即将到来的冠状病毒版本的前瞻性通用抑制特性。
DOI：
10.1021/acsomega.2c08073
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发表时间：
2023-10-03
期刊：
影响因子：
4.1
通讯作者：
Abdalla, Mohnad
中科院分区：
文献类型：
--
作者：
Rabie, Amgad M.;Abdel-Dayem, Marwa A.;Abdalla, Mohnad
具有一些核苷结构特征的异喹啉衍生物被认为是有效治疗不同的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染及其后续疾病2019冠状病毒病（COVID-19）的候选选择。SLL-0197800是最近发现的一种异喹啉化合物，具有潜在的抗SARS-CoV-2及其先前毒株的强通用抗SARS病毒活性。SLL-0197800非特异性地击中不同冠状病毒的主要蛋白酶（Mpro）。在本研究中，我们测试了这种实验剂的先前发现扩展到包括任何冠状病毒的可能性，方法是同时破坏可变性较小的复制酶，如RNA依赖性RNA聚合酶（RdRp）蛋白以及3′至5′核糖核酸外切酶（ExoN）蛋白。体外抗RdRp/ExoN试验显示，SLL-0197800对冠状病毒复制具有强效抑制活性，抗RdRp和抗RdRp/ExoN EC 50值极小（分别约为0.16和0.27 μM）。初步计算机模拟结果显著支持这些生化结果。简而言之，这些扩展工作目前的重要结果极大地加强和扩展了SLL-0197800之前的发现，表明限制/阻止行为（即，这种新的研究性抗SARS-CoV-2药物对Mpro蛋白的抑制活性）可以显著延长对其他复制和增殖酶如RdRp和ExoN的作用，突出了SLL-0197800对杀人冠状病毒的未来版本（如果有的话）的潜在用途，即，揭示了这种黄金实验药物对几乎任何冠状病毒株（例如SARS-CoV-3）的可能非特异性冠状病毒特征和质量。
Isoquinoline derivatives having some nucleosidic structural features are considered as candidate choices for effective remediation of the different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their following disease, the coronavirus disease 2019 (COVID-19). SLL-0197800 is a recently discovered isoquinoline compound with potential strong universal anticoronaviral activities against SARS-CoV-2 and its previous strains. SLL-0197800 nonspecifically hits the main protease (Mpro) enzyme of the different coronaviruses. Herein in the present study, we tested the probability of the previous findings of this experimental agent to be extended to comprise any coronavirus through concurrently disrupting the mutable-less replication enzymes like the RNA-dependent RNA polymerase (RdRp) protein as well as the 3′-to-5′ exoribonuclease (ExoN) protein. The in vitro anti-RdRp/ExoN assay revealed the potent inhibitory activities of SLL-0197800 on the coronaviral replication with minute values of anti-RdRp and anti-RdRp/ExoN EC50 (about 0.16 and 0.27 μM, respectively). The preliminary in silico outcomes significantly supported these biochemical findings. To put it simply, the present important results of these extension efforts greatly reinforce and extend the SLL-0197800’s preceding findings, showing that the restraining/blocking actions (i.e., inhibitory activities) of this novel investigational anti-SARS-CoV-2 agent against the Mpro protein could be significantly extended against other copying and multiplication enzymes such as RdRp and ExoN, highlighting the potential use of SLL-0197800 against the coming versions of the homicidal coronavirus (if any), i.e., revealing the probable nonspecific anticoronaviral features and qualities of this golden experimental drug against nearly any coronaviral strain, for instance, SARS-CoV-3.
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影响因子：
4.1
作者：
Rabie AM
通讯作者：
Rabie AM
影响因子：
3.7
作者：
Ip A;Ahn J;Zhou Y;Goy AH;Hansen E;Pecora AL;Sinclaire BA;Bednarz U;Marafelias M;Sawczuk IS;Underwood JP 3rd;Walker DM;Prasad R;Sweeney RL;Ponce MG;La Capra S;Cunningham FJ;Calise AG;Pulver BL;Ruocco D;Mojares GE;Eagan MP;Ziontz KL;Mastrokyriakos P;Goldberg SL
通讯作者：
Goldberg SL
影响因子：
3.8
作者：
Rabie AM
通讯作者：
Rabie AM
DOI：
10.1073/pnas.2106379119
发表时间：
2022-03-01
影响因子：
11.1
作者：
Moeller NH;Shi K;Demir Ö;Belica C;Banerjee S;Yin L;Durfee C;Amaro RE;Aihara H
通讯作者：
Aihara H
影响因子：
2.6
作者：
Rabie, Amgad M.;Eltayb, Wafa A.
通讯作者：
Eltayb, Wafa A.