PDF(Pubmed)
Abstract：
The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world. Covid-19 does an irreparable harm to the health and life of people. It also has a negative financial impact on the economies of most countries of the world. In this regard, the issue of creating drugs aimed at combating this disease is especially acute. In this work, molecular docking was used to study the docking of 23 compounds with QRF3a SARS-CoV2. The performed in silico modeling made it possible to identify leading compounds capable of exerting a potential inhibitory and virucidal effect. The leading compounds include chlorin (a drug used in PDT), iron(III)protoporphyrin (endogenous porphyrin), and tetraanthraquinone porphyrazine (an exogenous substance). Having taken into consideration the localization of ligands in the QRF3a SARS-CoV2, we have made an assumption about their influence on the pathogenesis of Covid-19. The interaction of chlorin, iron(III)protoporphyrin and protoporphyrin with the viral protein ORF3a were studied by fluorescence and UV-Vis spectroscopy. The obtained experimental results confirm the data of molecular docking. The results showed that a viral protein binds to endogenous porphyrins and chlorins, moreover, chlorin is a competitive ligand for endogenous porphyrins. Chlorin should be considered as a promising drug for repurposing.
摘要：
由冠状病毒（SARS-CoV2）引起的大流行性传染病（Covid-19）正在全球迅速传播。新冠肺炎对人们的健康和生命造成了不可挽回的伤害。它还对世界上大多数国家的经济产生负面的金融影响。在这方面,创造旨在对抗这种疾病的药物的问题尤其严重。在这项工作中,利用分子对接技术研究了23种化合物与QRF3aSARS-CoV2的对接。进行的计算机模拟使鉴定能够发挥潜在抑制和杀病毒作用的前导化合物成为可能。主要化合物包括二氢卟啉（PDT中使用的药物），铁（III）原卟啉（内源性卟啉），和四蒽醌卟啉（一种外源物质）。考虑到配体在QRF3aSARS-CoV2中的定位，我们假设了它们对Covid-19发病机理的影响。二氢卟啉的相互作用，通过荧光和紫外可见光谱研究了铁（III）和原卟啉与病毒蛋白ORF3a的关系。获得的实验结果证实了分子对接的数据。结果表明，病毒蛋白与内源性卟啉和二氢卟啉结合，此外,二氢卟啉是内源性卟啉的竞争性配体。应该考虑将氯苷作为一种有希望的再利用药物。
