Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.
Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.
复制标题
DOI：
10.1128/spectrum.01056-22
复制
发表时间：
2022-10-26
影响因子：
3.7
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Huang, Changbai;Feng, Fei;Shi, Yongxia;Li, Wenhui;Wang, Ziqiao;Zhu, Yunkai;Yuan, Shuai;Hu, Dandan;Dai, Jun;Jiang, Qiqi;Zhang, Rong;Liu, Chao;Zhang, Ping
严重急性呼吸综合征相关冠状病毒2型（SARS-CoV-2）感染已对全球公共卫生构成严重威胁。目前的研究表明，几种蛋白激酶C（PKC）抑制剂对SARS-CoV-2感染具有保护作用。四个泛蛋白激酶C抑制剂，Go 6983，双吲哚马来酰亚胺I，enzavelin，sotravelin，减少复制的SARS冠状病毒-2复制子在BHK-21和Huh 7细胞。PKCδ特异性抑制剂rottlerin也能有效减少病毒感染。PKC抑制剂在SARS-CoV-2感染的早期阶段起作用。最后，PKC抑制剂阻断野生型SARS-CoV-2在表达ACE 2的A549细胞中的复制。我们的工作突出了PKC信号通路在SARS-CoV-2感染中的重要性，并为PKC特异性抑制剂是抗SARS-CoV-2的潜在治疗药物提供了证据。目前迫切需要有效的治疗药物来控制严重急性呼吸综合征相关冠状病毒2（SARS-CoV-2）引起的大流行。我们发现，蛋白激酶C（PKC）的几种抑制剂显着降低SARS-CoV-2在培养细胞中的复制。这些PKC抑制剂干扰病毒感染的早期步骤。因此，PKC抑制剂的快速和显著的抗病毒作用强调了它们是有希望的抗病毒药物，并表明PKC是参与SARS-CoV-2感染的重要宿主因子。
Infection by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has posed a severe threat to global public health. The current study revealed that several inhibitors of protein kinases C (PKCs) possess protective activity against SARS-CoV-2 infection. Four pan-PKC inhibitors, Go 6983, bisindolylmaleimide I, enzastaurin, and sotrastaurin, reduced the replication of a SARS-CoV-2 replicon in both BHK-21 and Huh7 cells. A PKCδ-specific inhibitor, rottlerin, was also effective in reducing viral infection. The PKC inhibitors acted at an early step of SARS-CoV-2 infection. Finally, PKC inhibitors blocked the replication of wild-type SARS-CoV-2 in ACE2-expressing A549 cells. Our work highlights the importance of the PKC signaling pathway in infection by SARS-CoV-2 and provides evidence that PKC-specific inhibitors are potential therapeutic agents against SARS-CoV-2. IMPORTANCE There is an urgent need for effective therapeutic drugs to control the pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). We found that several inhibitors of protein kinases C (PKCs) dramatically decrease the replication of SARS-CoV-2 in cultured cells. These PKC inhibitors interfere with an early step of viral infection. Therefore, the rapid and prominent antiviral effect of PKC inhibitors underscores that they are promising antiviral agents and suggests that PKCs are important host factors involved in infection by SARS-CoV-2.
登录
查看更多内容
影响因子：
5.4
作者：
Kawano T;Inokuchi J;Eto M;Murata M;Kang JH
通讯作者：
Kang JH
影响因子：
--
作者：
Nakagawa K;Lokugamage KG;Makino S
通讯作者：
Makino S
影响因子：
7.7
作者：
Mondal A;Dawson AR;Potts GK;Freiberger EC;Baker SF;Moser LA;Bernard KA;Coon JJ;Mehle A
通讯作者：
Mehle A
DOI：
10.3390/antibiotics10111294
发表时间：
2021-10-23
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Lee CC;Hsieh CC;Ko WC
通讯作者：
Ko WC
影响因子：
5
作者：
Gorbalenya AE;Enjuanes L;Ziebuhr J;Snijder EJ
通讯作者：
Snijder EJ