Theoretical and experimental study of interaction of macroheterocyclic compounds with ORF3a of SARS-CoV-2

Natalia Sh. Lebedeva,Galina M. Mamardashvili,Julia V. Romanenko,Sergey A. Zdanovich,Oskar I. Koifman,Mikhail O. Koifman,Yury A. Gubarev,Svetlana V. Zaitceva,Alena S. Malyasova

doi:10.1038/s41598-021-99072-8

Natalia Sh. Lebedeva, Galina M. Mamardashvili + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-99072-8

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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.

Highlights

The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world
Most of the ORF3a coronaviruses proteins function in a dimeric form, about 10% of these proteins are tetramers[27,33], the macroheterocyclic tetrapyrrole compounds (MHCs) was docked to the ORF3a SARS-CoV-2 dimer
Experimental studies of the interaction of the viral protein ORF3a with exogenous porphyrins and chlorin, a drug used for PDT, have been carried out

Summary

Introduction

The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world. The high mutation rate of RNA viruses, combined with short generation time and large population sizes, allows the virus to develop rapidly and adapt to the host environment. This causes difficulties in the development of vaccines and antiviral drugs. Drugs and treatment protocols that provide an inhibitory, and a virucidal effect are considered to be the most promising This is precisely the effect of macroheterocyclic tetrapyrrole compounds (MHCs) which are capable of generating singlet oxygen or other active radicals under the action of light, thereby oxidizing RNA or virus proteins

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