Spectral and theoretical study of SARS-CoV-2 ORF10 protein interaction with endogenous and exogenous macroheterocyclic compounds

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.

Keywords: Accessory proteins; Chlorin; Molecular docking; ORF10; Porphyrin; SARS-CoV-2; Spectroscopy.