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Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses

机译:瑞德西韦衍生物 VV116 是人类和动物冠状病毒的潜在广谱抑制剂

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摘要

Coronaviruses represent a significant threat to both human and animal health, encompassing a range of pathogenic strains responsible for illnesses, from the common cold to more severe diseases. VV116 is a deuterated derivative of Remdesivir with oral bioavailability that was found to potently inhibit SARS-CoV-2. In this work, we investigated the broad-spectrum antiviral activity of VV116 against a variety of human and animal coronaviruses. We examined the inhibitory effects of VV116 on the replication of the human coronaviruses HCoV-NL63, HCoV-229E, and HCoV-OC43, as well as the animal coronaviruses MHV, FIPV, FECV, and CCoV. The findings reveal that VV116 effectively inhibits viral replication across these strains without exhibiting cytotoxicity, indicating its potential for safe therapeutic use. Based on the results of a time-of-addition assay and an rNTP competitive inhibition assay, it is speculated that the inhibitory mechanism of VV116 against HCoV-NL63 is consistent with its inhibition of SARS-CoV-2. Our work presents VV116 as a promising candidate for broad-spectrum anti-coronavirus therapy, with implications for both human and animal health, and supports the expansion of its therapeutic applications as backed by detailed experimental data.
机译:冠状病毒对人类和动物健康构成重大威胁,包括一系列导致疾病的致病菌株,从普通感冒到更严重的疾病。VV116 是瑞德西韦的氘代衍生物,具有口服生物利用度,被发现可有效抑制 SARS-CoV-2。在这项工作中,我们研究了 VV116 对多种人类和动物冠状病毒的广谱抗病毒活性。我们研究了 VV116 对人类冠状病毒 HCoV-NL63 、 HCoV-229E 和 HCoV-OC43 以及动物冠状病毒 MHV 、 FIPV 、 FECV 和 CCoV 复制的抑制作用。研究结果表明,VV116 有效抑制了这些菌株中的病毒复制,而没有表现出细胞毒性,表明其具有安全治疗的潜力。根据添加时间测定和 rNTP 竞争性抑制试验的结果,推测 VV116 对 HCoV-NL63 的抑制机制与其对 SARS-CoV-2 的抑制一致。我们的工作将 VV116 视为广谱抗冠状病毒疗法的有前途的候选药物,对人类和动物健康都有影响,并在详细实验数据的支持下支持其治疗应用的扩展。

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