鉴定已批准药物中可用于抑制新冠病毒进入细胞的药物。

Identification of SARS-CoV-2 entry inhibitors among already approved drugs.

机构信息

Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

出版信息

Acta Pharmacol Sin. 2021 Aug;42(8):1347-1353. doi: 10.1038/s41401-020-00556-6. Epub 2020 Oct 28.

DOI:10.1038/s41401-020-00556-6

PMID:33116249

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7594953/

Abstract

To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC = 0.95 ± 0.83 µM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.

摘要

为了在已批准的临床药物中发现治疗 COVID-19 的有效药物，我们使用 SARS-CoV-2 假病毒开发了一种用于 SARS-CoV-2 病毒进入抑制剂的高通量筛选测定法。对 1800 种小分子药物的批准药物库进行了 SARS2 进入抑制剂的筛选，发现 15 种活性药物可特异性抑制 SARS2- pseudovirus 进入。使用 Vero E6 细胞中的天然 SARS-CoV-2 病毒进行的抗病毒测试证实，其中 7 种药物（氯苯那敏、胺碘酮、曲美嗪、博舒替尼、托瑞米芬、氟哌噻吨和氮卓斯汀）显著抑制了 SARS2 的复制，使上清液中病毒 RNA 载量减少，具有很有前途的活性水平。这 3 种药物被归类为组胺受体拮抗剂，其中氯苯那敏显示出最强的抗 SARS2 活性（EC = 0.95 ± 0.83 μM）。我们的工作表明，这 7 种药物可能会进一步进入 COVID-19 治疗的体内研究和临床研究。