Screening for inhibitors against SARS-CoV-2 and its variants.
Screening for inhibitors against SARS-CoV-2 and its variants.
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DOI：
10.1016/j.bsheal.2022.05.002
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发表时间：
2022-06
影响因子：
--
通讯作者：
Wang, Jianwei
中科院分区：
文献类型：
--
作者：
Yuan, Weijing;Dong, Xiaojing;Chen, Lan;Lei, Xiaobo;Zhou, Zhuo;Guo, Li;Wang, Jianwei
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）继续演变，产生对全球健康构成威胁的新变种；因此，必须获得针对SARS-CoV-2及其变体的安全、广谱抗病毒药物。为此，我们筛选了能够抑制病毒进入的化合物，这是病毒感染的关键步骤。使用含有原始菌株（SARS-CoV-2- wh01）刺突蛋白的假病毒对以前报道的抑制SARS-CoV-2复制的20种化合物进行了测试。测定了这些化合物的细胞毒性。此外，我们还鉴定出6种对WH01假病毒具有较强拮抗活性的化合物，并鉴定出较低的细胞毒性。然后评估这些化合物对表达B.1.617.2 （Delta）和B.1.1.529 （Omicron）两种最流行的流行毒株刺突蛋白的假病毒的功效。这些实验表明，两种吩噻嗪类化合物三氟拉嗪2HCl和硫硝嗪HCl可以抑制Delta和Omicron假病毒的感染。最后，我们发现这两种化合物对真正的SARS-CoV-2病毒非常有效，包括WH01、Delta和Omicron菌株。我们的研究确定了潜在的广谱SARS-CoV-2抑制剂，并为开发新的治疗方法提供了见解。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.
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影响因子：
7.3
作者：
Xiao X;Wang C;Chang D;Wang Y;Dong X;Jiao T;Zhao Z;Ren L;Dela Cruz CS;Sharma L;Lei X;Wang J
通讯作者：
Wang J
影响因子：
7
作者：
Boisson-Dupuis S;Kong XF;Okada S;Cypowyj S;Puel A;Abel L;Casanova JL
通讯作者：
Casanova JL
影响因子：
7.6
作者：
Choy, Ka-Tim;Wong, Alvina Yin-Lam;Yen, Hui-Ling
通讯作者：
Yen, Hui-Ling
FDA 批准的几种药物可在体外有效抑制 SARS-CoV-2 感染
影响因子：
5.6
作者：
Xiong HL;Cao JL;Shen CG;Ma J;Qiao XY;Shi TS;Ge SX;Ye HM;Zhang J;Yuan Q;Zhang TY;Xia NS
通讯作者：
Xia NS
影响因子：
6.1
作者：
Elfiky, Abdo A.
通讯作者：
Elfiky, Abdo A.