Abstract：
The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 coronavirus has spread rapidly around the world in a matter of weeks. Most of the current recommendations developed for the use of antivirals in COVID-19 were developed during the initial waves of the pandemic, when resources were limited and administrative or pragmatic criteria took precedence. The choice of drugs for the treatment of COVID-19 was carried out from drugs approved for medical use. COVID-19 is a serious public health problem and the search for drugs that can relieve the disease in infected patients at various stages is still necessary. Therefore, the search for effective drugs with inhibitory and/or virucidal activity is a paramount task. Accessory proteins of the virus play a significant role in the pathogenesis of the disease, as they modulate the host\'s immune response. This paper studied the interaction of one of the SARS-CoV-2 accessory proteins ORF10 with macroheterocyclic compounds - protoporphyrin IX d.m.e., Fe(III)protoporphyrin d.m.e. and 5,10,15,20-tetrakis(3\'-pyridyl)chlorin tetraiodide, which are potential inhibitors and virucidal agents. The SARS-CoV-2 ORF10 protein shows the highest affinity for Chlorin, which binds hydrophobically to the alpha structured region of the protein. Protoporphyrin is able to form several complexes with ORF10 close in energy, with alpha- and beta-molecular recognition features, while Fe(III)protoporphyrin forms complexes with the orientation of the porphyrin macrocycle parallel to the ORF10 alpha-helix. Taking into account the nature of the interaction with ORF10, it has been suggested that Chlorin may have virucidal activity upon photoexposure. The SARS-CoV-2 ORF10 protein was expressed in Escherichia coli cells, macroheterocyclic compounds were synthesized, and the structure was confirmed. The interaction between macrocycles with ORF10 was studied by spectral methods. The results of in silico studies were confirmed by experimental data.
摘要：
由SARS-CoV-2冠状病毒引起的2019年冠状病毒病（COVID-19）在几周内迅速在世界各地传播。目前为在COVID-19中使用抗病毒药物制定的大多数建议都是在大流行的最初浪潮中制定的，当资源有限，行政或务实标准优先时。用于治疗COVID-19的药物的选择是从批准用于医疗用途的药物中进行的。COVID-19是一个严重的公共卫生问题，寻找可以在不同阶段缓解感染患者疾病的药物仍然是必要的。因此,寻找具有抑制和/或杀病毒活性的有效药物是一项至关重要的任务。病毒的辅助蛋白在疾病的发病机理中起着重要作用，因为它们调节宿主的免疫反应。本文研究了SARS-CoV-2辅助蛋白ORF10与大杂环化合物-原卟啉IXd.m.e.的相互作用，Fe（III）原卟啉d.m.e.和5,10,15,20-四（3'-吡啶基）氯四碘化物，它们是潜在的抑制剂和杀病毒剂。SARS-CoV-2ORF10蛋白对氯色素的亲和力最高，与蛋白质的α结构区域疏水结合。原卟啉能够与能量接近的ORF10形成几种配合物，具有α-和β-分子识别特征，而Fe（III）原卟啉形成络合物，卟啉大环的方向平行于ORF10α-螺旋。考虑到与ORF10的相互作用的性质,已经提出了氯色素在光暴露时可能具有杀病毒活性。SARS-CoV-2ORF10蛋白在大肠杆菌细胞中表达,合成了大杂环化合物，结构得到确认。通过光谱方法研究了大环与ORF10之间的相互作用。实验数据证实了计算机模拟研究的结果。
