The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC₅₀ values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC₅₀ value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC₅₀ > 100 μM) also had higher biological safety for host cells than honokiol (TC₅₀ of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

中文翻译：

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含有 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones 的和厚朴酚衍生物作为抗 SARS-CoV-2 的潜在病毒进入抑制剂的合成和生物学评价

由 SARS-CoV-2 病毒感染引起的 2019 冠状病毒病 (COVID-19) 对全球健康和经济构成了严重威胁。然而，特异性和有效的 SARS-CoV-2 药物仍在开发中。Honokiol 是一种来自厚朴的生物活性成分，具有燥湿作用。为了开发新的有效抗病毒分子，通过引入各种 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2( 3H )-ones合成了一系列新的和厚朴酚类似物。它的分子。在 SARS-CoV-2 假病毒模型中，检查了所有和厚朴酚衍生物的抗病毒进入活性。结果，6a和6p证明了 IC _{50 的}抗病毒进入作用值分别为 29.23 和 9.82 µM。然而，亲本和厚朴酚具有非常弱的抗病毒活性，IC ₅₀值超过 50 µM。生物层干涉仪 (BLI) 结合测定和分子对接研究表明，6p与人 ACE2 蛋白的结合比亲代和厚朴酚具有更高的结合亲和力和更低的结合能。一项竞争性 ELISA 测定证实了6p对 SARS-CoV-2 尖峰 RBD 与 ACE2 的结合具有抑制作用。重要的是，6a和6p (TC ₅₀ > 100 μM) 对宿主细胞的生物安全性也高于和厚朴酚 (TC ₅₀48.23 μM）。这项研究可能有助于发现 SARS-CoV-2 病毒的潜在病毒入口抑制剂，尽管6p的抗病毒功效需要在生物安全 3 级设施中对 SARS-CoV-2 病毒株进行验证。