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.
摘要：
鉴于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新变种不断涌现，开发新的抑制剂是必要的，以提高临床疗效和增加联合治疗冠状病毒疾病2019的选择。因为海洋生物一直是发现许多生物活性分子的资源，我们建立了从冲绳群岛收集的海洋无脊椎动物的提取物库。在这项研究中,提取物用于鉴定抗SARS-CoV-2的抗病毒分子。在VeroE6/TMPRSS2细胞中使用细胞病变效应（CPE）测定法，来自海洋海绵Theonellaswinhoei的提取物被发现可以减少病毒诱导的CPE。最终,使用柱层析和NMR分析鉴定了在提取物中的一种抗病毒化合物。OnnamideA抑制了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的病毒产生。此外，这种化合物阻止了SARS-CoV-2伪病毒粒子的进入。一起来看,这些结果表明，甲胺抑制SARS-CoV-2感染，这可能部分与进入抑制有关，并有望成为抗SARS-CoV-2药物开发的候选先导化合物。
