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发现诃子酸和石榴皮苷为新型严重急性呼吸综合征冠状病毒2 3CL的变构抑制剂。

Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CL.

作者信息

Du Ruikun, Cooper Laura, Chen Zinuo, Lee Hyun, Rong Lijun, Cui Qinghua

机构信息

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China.

Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.

出版信息

Antiviral Res. 2021 Jun;190:105075. doi: 10.1016/j.antiviral.2021.105075. Epub 2021 Apr 17.

Abstract

The emerging SARS-CoV-2 infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Both CHLA and PUG reduced virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic concentrations, by targeting the enzymatic activity of viral 3-chymotrypsin-like cysteine protease (3CL) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies.

摘要

新出现的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染是全球新冠肺炎大流行的病因。迄今为止,对抗这种疾病的治疗选择有限。在此,我们研究了两种广谱抗病毒天然产物诃子鞣酸(CHLA)和石榴皮鞣质(PUG)对SARS-CoV-2病毒复制的抑制能力。CHLA和PUG在无细胞毒性浓度下,通过靶向病毒3-糜蛋白酶样半胱氨酸蛋白酶(3CL)的酶活性作为变构调节剂,减少了病毒在Vero-E6单层细胞中诱导的蚀斑形成。我们的研究证明了CHLA和PUG作为新型新冠肺炎治疗药物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c51c/8052511/66918f5aa26e/gr1_lrg.jpg

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