What binds cationic photosensitizers better: Brownian dynamics reveals key interaction sites on spike proteins of sars-cov, mers-cov, and sars-cov-2

We compared the electrostatic properties of the spike proteins (S-proteins) of three coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, and their interactions with photosensitizers (PSs), octacationic octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) and monocationic methylene blue (MB). We found a major common PS binding site at the connection of the S-protein stalk and head. The molecules of Zn-PcChol8+ and MB also form electrostatic encounter complexes with large area of negative electrostatic potential at the head of the S-protein of SARS-CoV-2, between fusion protein and heptad repeat 1 domain. The top of the SARS-CoV spike head demonstrates a notable area of electrostatic contacts with Zn-PcChol8+ and MB that corresponds to the N-terminal domain. The S-protein protomers of SARS-CoV-2 in “open” and “closed” conformations demonstrate different ability to attract PS molecules. In contrast with Zn-PcChol8+, MB possesses the ability to penetrate inside the pocket formed as a result of SARS-CoV-2 receptor binding domain transition into the “open” state. The existence of binding site for cationic PSs common to the S-proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV creates prospects for the wide use of this type of PSs to combat the spread of coronaviruses. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Fedorov V.1 , Kholina E.1 , Khruschev S.1 , Kovalenko I. 1, 2, 3, 4, 5, 6 , Rubin A.1 , Strakhovskaya M.1, 2
Journal
Publisher
MDPI AG
Number of issue
8
Language
English
Status
Published
Number
1615
Volume
13
Year
2021
Organizations
  • 1 Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russian Federation
  • 2 Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia, Moscow, 115682, Russian Federation
  • 3 Institute for Persolanized Medicine, Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russian Federation
  • 4 Institute of Physics and Mathematics, Astrakhan State University, Astrakhan, 414056, Russian Federation
  • 5 Scientific and Technological Center of Unique Instrumentation of the Russian Academy of Sciences, Moscow, 117342, Russian Federation
  • 6 S.M. Nikolskii Mathematical Institute, Peoples’ Friendship, University of Russia (RUDN University), Moscow, 117198, Russian Federation
Keywords
Brownian dynamics; MERS-CoV; Methylene blue; Octakis(cholinyl)zinc phthalocyanine; Photosensitizer; SARS-CoV; SARS-CoV-2; Spike protein
Date of creation
16.12.2021
Date of change
16.12.2021
Short link
https://repository.rudn.ru/en/records/article/record/76710/
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