Drupacine as a potent SARS-CoV-2 replication inhibitor in vitro

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
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引用次数: 0

Abstract

Despite the availability of vaccines and antiviral treatments, the continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and breakthrough infections underscores the need for new, potent antiviral therapies. In a previous study, we established a transcription and replication-competent SARS-CoV-2 virus-like particle (trVLP) system that recapitulates the complete viral life cycle. In this study, we combined high-content screening (HCS) with the SARS-CoV-2 trVLP cell culture system, providing a powerful phenotype-oriented approach to assess the antiviral potential of compounds on a large scale. We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS-CoV-2 infection. Furthermore, we utilized a SARS-CoV-2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication. However, in vitro, enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets, such as the viral non-structural proteins nsp5 (MPro) or nsp12 (RdRp). In conclusion, our findings position drupacine as a promising antiviral candidate against SARS-CoV-2, providing a novel scaffold for developing anti-coronavirus disease 2019 therapeutics. Further investigation is required to pinpoint its precise target and mechanism of action.
杜拉辛是一种有效的 SARS-CoV-2 体外复制抑制剂
尽管已经有了疫苗和抗病毒治疗方法,但严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)变种和突破性感染的不断出现凸显了对新型强效抗病毒疗法的需求。在之前的一项研究中,我们建立了一个转录和复制能力强的 SARS-CoV-2 病毒样颗粒(trVLP)系统,该系统再现了病毒的完整生命周期。在本研究中,我们将高内涵筛选(HCS)与 SARS-CoV-2 trVLP 细胞培养系统相结合,提供了一种以表型为导向的强大方法来大规模评估化合物的抗病毒潜力。我们筛选了一个包含 3,200 种天然化合物的化合物库,发现 drupacine 是一种潜在的抗 SARS-CoV-2 感染候选化合物。此外,我们还利用 SARS-CoV-2 复制子系统证明了 drupacine 可抑制病毒基因组转录和复制。然而,体外酶学测定显示,这种抑制作用不能归因于传统的抗病毒靶点,如病毒非结构蛋白 nsp5(MPro)或 nsp12(RdRp)。总之,我们的研究结果将 drupacine 定位为一种很有前景的 SARS-CoV-2 候选抗病毒药物,为 2019 年开发抗冠状病毒疾病疗法提供了一个新的支架。要确定其精确靶点和作用机制,还需要进一步研究。
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
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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