抗SARS-COV-2感染的维生素药物偶联物的设计与合成

R. Bhole, P.M. Karche, Y. Shinde, P. Kute, S. Gurav, R. Wavhale
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引用次数: 0

摘要

新型冠状病毒感染由于传播迅速,已成为全球流行病。因此,迫切需要治疗COVID-19患者。本研究的目的是假设和检验维生素药物缀合物作为靶向片段。由于其抗菌、抗氧化和免疫调节活性,该支架可能具有对抗COVID-19感染的潜在作用。在这里,我们强调了维生素维生素药物偶联物作为SARS-COV-2感染的可能治疗方法。因此,我们通过酯化机制合成、表征并评价了羟氯喹-叶酸偶联物(HCQ-FA),通过协同机制增强治疗效果,掩盖不良副作用,改善细胞内化,从而有效治疗SARS-CoV-2感染。利用前药可以提高现有抗病毒药物的疗效和生物利用度。通过红外、核磁共振、质谱等光谱数据对共轭物的结构进行了表征,表明HCQ-FA共轭物是由三元共轭形成的。分子对接研究表明,HCQ-FA偶联物与主要蛋白酶片段具有良好的对接和结合相互作用。分子动力学刺激结果表明,该偶联物在SARS主要蛋白酶片段结合位点具有良好的稳定性,对COVID-19感染具有抑制活性。
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Design and Synthesis of Vitamin Drug Conjugate for its Probable Potential Against SARS-COV-2 Infections
The novel corona virus infection had become a global epidemic due to its rapid spread. So, there is an urgent need to treat COVID-19 patients. The aim of this research was to hypothesize and examine vitamin drug con-jugate as targeted moiety. The present scaffold may have potential role to fight against COVID-19 infection due to its antimicrobial, antioxidants and immunomodulatory activities. Here, we've highlighted the term Vit-amin Drug Conjugate as possible therapy approach for SARS-COV-2 infection. As a result, we synthesize, characterized, and evaluated a Hydroxychloroquine — Folic Acid conjugate (HCQ-FA) by esterification mechanism to provide effective treatment against SARS-CoV-2 infection by enhancing therapeutic effect through synergistic mechanism, masking undesired side effects, and improving cellular internalization. By us-ing prodrug, the efficacy and bioavailability of existing antiviral drugs could be improved. The structure of the conjugate was determined by spectroscopic data like IR, NMR, and mass spectra, which indicates that HCQ-FA conjugate formed by esteric conjugation. Molecular docking studies revealed that HCQ-FA conju-gate shows good level of docking as well as binding interaction with main protease moiety. Molecular dy-namic stimulation revealed that this conjugate shows good stability at the binding site of SARS main protease moiety and exhibits inhibitory activity against COVID-19 infection.
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