Vitamin D deficiency significantly correlates with the severity of SARS-COV-2 infection. Molecular docking-based virtual screening studies predict that novel vitamin D and related lumisterol hydroxymetabolites are able to bind to the active sites of two SARS-COV-2 transcription machinery enzymes with high affinity. These enzymes are the main protease (M^pro) and RNA dependent RNA polymerase (RdRP) which play important roles in viral replication and establishing infection. Based on predicted binding affinities and specific interactions, we identified ten D3 and lumisterol analogs as likely binding partners of SARS-CoV-2 M^pro and RdRP and therefore tested their ability to inhibit these enzymes. Activity measurements demonstrated that 25(OH)L3, 24(OH)L3 and 20(OH)7DHC are the most effective of the hydroxymetabolites tested at inhibiting the activity of SARS-CoV-2 M^pro, causing 10-19% inhibition. These same derivatives as well as other hydroxylumisterols and hydroxyvitamin D3 metabolites inhibited RdRP by 50-60%. Thus, inhibition of these enzymes by vitamin D and lumisterol metabolites may provide a novel approach to hindering the SARS-COV-2 infection.

中文翻译：

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维生素D和lumisterol新代谢物可抑制SARS-COV-2复制机械酶

维生素 D 缺乏与 SARS-COV-2 感染的严重程度显着相关。基于分子对接的虚拟筛选研究预测，新型维生素 D 和相关的光甾醇羟基代谢物能够以高亲和力与两种 SARS-COV-2 转录机器酶的活性位点结合。这些酶是主要的蛋白酶 (M ^pro ) 和 RNA 依赖性 RNA 聚合酶 (RdRP)，它们在病毒复制和感染建立中起重要作用。基于预测的结合亲和力和特定的相互作用，我们确定了 10 个 D3 和 lumisterol 类似物作为 SARS-CoV-2 M ^{pro 的}可能结合伙伴和 RdRP，因此测试了它们抑制这些酶的能力。活性测量表明，25(OH)L3、24(OH)L3 和 20(OH)7DHC 是经测试的最有效的抑制 SARS-CoV-2 M ^pro活性的羟基代谢物，导致 10-19% 的抑制。这些相同的衍生物以及其他羟基磷灰石醇和羟基维生素 D3 代谢物将 RdRP 抑制了 50-60%。因此，通过维生素 D 和 lumisterol 代谢物抑制这些酶可能提供一种阻止 SARS-COV-2 感染的新方法。