Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12

Abstract

Background: The outbreak and continued spread of coronavirus infection (COVID-19) sets the goal of finding new tools and methods to develop analytical procedures and tests to detect, study infection and prevent morbidity.

Methods: The noncovalent binding of cyanine and squarylium dyes of different classes (60 compounds in total) with the proteases NSP3, NSP5, and NSP12 of SARS-CoV-2 was studied by the method of molecular docking.

Results: The interaction energies and spatial configurations of dye molecules in complexes with NSP3, NSP5, and NSP12 have been determined.

Conclusion: A number of anionic dyes showing lower values of the total energy E_tot could be recommended for practical research in the development of agents for the detection and inactivation of the coronavirus.

Author summary

Using molecular docking modeling, the noncovalent interaction of a large number of cyanine and squarylium dyes of various classes with SARS-CoV-2 coronavirus proteases has been studied. It has been found that electrostatic ligand–protein interactions (Coulomb interactions) can play an important role in the stability of noncovalent complexes. Based on the data obtained, the selection of dyes for further practical research has been carried out with the aim of developing spectral-fluorescent probes for detection of SARS-CoV-2. In addition, it is concluded that mesosubstituted thiacarbocyanines may be promising for use in photoinactivation of the coronavirus.

Graphical abstract

Keywords

SARS-CoV-2 / proteases / polymethine dyes / squarylium dyes / noncovalent interaction / molecular docking

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ACKNOWLEDGEMENTS

The work was carried out under the Russian Federation State Assignment (state registration No. 001201253314; Institute of Biochemical Physicas, Russian Academy of Sciences). Molecular graphics and analyses performed with UCSF Chimera are developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Pavel Pronkin and Alexander Tatikolov declare that they have no conflict of interests. All procedures performed in studies were in accordance with the ethical standards of the institution or practice at which the studies were conducted, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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