Onnamide A suppresses the severe acute respiratory syndrome-coronavirus 2 infection without inhibiting 3-chymotrypsin-like cysteine protease.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yasuhiro Hayashi, Nanami Higa, Tetsuro Yoshida, Trianda Ayuning Tyas, Kanami Mori-Yasumoto, Mina Yasumoto-Hirose, Hideki Tani, Junichi Tanaka, Takahiro Jomori
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引用次数: 0

Abstract

Given the continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of new inhibitors is necessary to enhance clinical efficacy and increase the options for combination therapy for the coronavirus disease 2019. Because marine organisms have been a resource for the discovery of numerous bioactive molecules, we constructed an extract library of marine invertebrates collected from the Okinawa Islands. In this study, the extracts were used to identify antiviral molecules against SARS-CoV-2. Using a cytopathic effect (CPE) assay in VeroE6/TMPRSS2 cells, an extract from the marine sponge Theonella swinhoei was found to reduce virus-induced CPE. Eventually, onnamide A was identified as an antiviral compound in the extract using column chromatography and NMR analysis. Onnamide A inhibited several SARS-CoV-2 variant-induced CPEs in VeroE6/TMPRSS2 cells as well as virus production in the supernatant of infected cells. Moreover, this compound blocked the entry of SARS-CoV-2 pseudo-virions. Taken together, these results demonstrate that onnamide A suppresses SARS-CoV-2 infection, which may be partially related to entry inhibition, and is expected to be a candidate lead compound for the development of anti-SARS-CoV-2 drugs.

翁内酰胺 A 可抑制严重急性呼吸系统综合征-冠状病毒 2 感染,而不会抑制 3-糜蛋白酶样半胱氨酸蛋白酶。
鉴于严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)新变种的不断出现,有必要开发新的抑制剂,以提高临床疗效,增加 2019 年冠状病毒疾病联合疗法的选择。由于海洋生物是发现大量生物活性分子的资源,我们构建了一个从冲绳群岛采集的海洋无脊椎动物提取物库。在这项研究中,我们利用这些提取物来鉴定针对 SARS-CoV-2 的抗病毒分子。通过在 VeroE6/TMPRSS2 细胞中进行细胞病理效应(CPE)试验,发现海洋海绵 Theonella swinhoei 的提取物可减少病毒诱导的 CPE。通过柱层析和核磁共振分析,最终确定翁酰胺 A 是提取物中的一种抗病毒化合物。Onnamide A 能抑制 VeroE6/TMPRSS2 细胞中几种 SARS-CoV-2 变体诱导的 CPE 以及感染细胞上清液中病毒的产生。此外,这种化合物还能阻止 SARS-CoV-2 伪病毒的进入。综上所述,这些结果表明昂纳米德 A 能抑制 SARS-CoV-2 感染,部分原因可能与抑制病毒进入有关,有望成为开发抗 SARS-CoV-2 药物的候选先导化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of biochemistry
Journal of biochemistry 生物-生化与分子生物学
CiteScore
4.80
自引率
3.70%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.
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