Prospects for the use of macrocyclic photosensitizers for inactivation of SARS-CoV-2: selection of compounds leaders based on the molecular docking data

Abstract

The treatment of coronavirus COVID-19, like other viral diseases, is currently underdeveloped. This fact necessitates the search for new drugs and treatment methods that will effectively disrupt the life cycle of the virus. A big problem in the therapy of viral diseases is the ability of viruses to evade the host's immune response. We suppose that the search for drugs that can change the evasiveness of the virus from the immune response of the host is a very promising strategy, as it can help the body to cope with the infection. Protein SARS-CoV-2 ORF8 is one of the key proteins that can suppress antiviral immunity. This paper considers the available information on the structure and functioning of ORF8, as well as the results of molecular docking of ORF8 to a wide range of tetrapyrrole macroheterocyclic compounds capable of generating reactive oxygen species upon photoirradiation. This principle of photoinactivation of biosubstrates underlies the methods of photodynamic therapy of cancer. Application of photoinactivation of drug-resistant forms of bacteria and some viruses can be useful in the fight against COVID-19 and other viral infections. In this work, the structure of ORF8 complexes with macrocyclic compounds is considered in detail, the dependence of their binding affinity on the nature of macrocycles and the nature of peripheral substituents is analyzed and spectral studies of the binding of ORF8 to chlorin is performed. This paper is a part of a large project to investigate the possibility of using macrocyclic compounds for the treatment of viral diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• molecular docking
• ORF8
• proteins
• porphyrins
• chlorin
• fluorescence
• UV–Vis

Acknowledgements

The work was supported by Russian Foundation for Basic Research, grant 20-04-60108.

Disclosure statement

The author(s) declare no competing interests.

Author contributions

The manuscript was written through contributions of all authors. Y.G. and N.L. Conceptualization, Writing – Original Draft, Writing – Review and Editing, Y.G., E.Y., S.V.Z., S.A.Z. and G.M. Investigation, Data Curation, Formal analysis, O.K. Funding acquisition, all authors reviewed the manuscript. All authors have given approval to the final version of the manuscript.