{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:08:05Z","timestamp":1784945285148,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["20-04-60084"],"award-info":[{"award-number":["20-04-60084"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-10055"],"award-info":[{"award-number":["19-74-10055"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Photodynamic inactivation of pathogenic microorganisms can be successfully used to eradicate pathogens in localized lesions, infected liquid media, and on various surfaces. This technique utilizes the photosensitizer (PS), light, and molecular oxygen to produce reactive oxygen species that kill pathogens. Here, we used the PS, water soluble octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+), to inactivate an initial 4.75\u20135.00 IgTCID50\/mL titer of SARS-CoV-2, thereby preventing viral infection when tested in Vero E6 cell cultures. Zn-PcChol8+ in a minimally studied concentration, 1 \u00b5M and LED 3.75 J\/cm2, completely destroyed the infectivity of SARS-CoV-2. To detect possible PS binding sites on the envelope of SARS-CoV-2, we analyzed electrostatic potential and simulated binding of Zn-PcChol8+ to the spike protein of this coronavirus by means of Brownian dynamics software, ProKSim (Protein Kinetics Simulator). Most of the Zn-PcChol8+ molecules formed clusters at the upper half of the stalk within a vast area of negative electrostatic potential. Positioning of the PS on the surface of the spike protein at a distance of no more than 10 nm from the viral membrane may be favorable for the oxidative damage. The high sensitivity of SARS-CoV-2 to photodynamic inactivation by Zn-PcChol8+ is discussed with respect to the application of this PS to control the spread of COVID-19.<\/jats:p>","DOI":"10.3390\/v13040643","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T21:47:33Z","timestamp":1618264053000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Photosensitizer Octakis(cholinyl)zinc Phthalocyanine with Ability to Bind to a Model Spike Protein Leads to a Loss of SARS-CoV-2 Infectivity In Vitro When Exposed to Far-Red LED"],"prefix":"10.3390","volume":"13","author":[{"given":"Kirill","family":"Sharshov","sequence":"first","affiliation":[{"name":"Federal Research Center of Fundamental and Translational Medicine (CFTM), 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Solomatina","sequence":"additional","affiliation":[{"name":"Federal Research Center of Fundamental and Translational Medicine (CFTM), 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kurskaya","sequence":"additional","affiliation":[{"name":"Federal Research Center of Fundamental and Translational Medicine (CFTM), 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-6591","authenticated-orcid":false,"given":"Ilya","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5918-5084","authenticated-orcid":false,"given":"Ekaterina","family":"Kholina","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9397-1548","authenticated-orcid":false,"given":"Vladimir","family":"Fedorov","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Meerovich","sequence":"additional","affiliation":[{"name":"Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Institute of Physics and Engineering in Biomedicine, National Research Nuclear University \u201cMEPHI\u201d, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Rubin","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-0431","authenticated-orcid":false,"given":"Marina","family":"Strakhovskaya","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies of the Federal Medical and Biological Agency of Russia, 115682 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S0140-6736(03)13077-2","article-title":"Coronavirus as a possible cause of severe acute respiratory syndrome","volume":"361","author":"Peiris","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7790","DOI":"10.1128\/JVI.01244-13","article-title":"Middle East respiratory syndrome coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group","volume":"87","author":"Baker","year":"2013","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.7150\/ijbs.45053","article-title":"SARS-CoV-2: An Emerging Coronavirus that Causes a Global Threat","volume":"16","author":"Zheng","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_4","first-page":"185","article-title":"Protection and disinfection policies against SARS-CoV-2 (COVID-19)","volume":"28","author":"Fathizadeh","year":"2020","journal-title":"Infez. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.it.2020.10.004","article-title":"Mechanisms of SARS-CoV-2 Transmission and Pathogenesis","volume":"41","author":"Harrison","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jhin.2020.01.022","article-title":"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents","volume":"104","author":"Kampf","year":"2020","journal-title":"J. Hosp. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110265","DOI":"10.1016\/j.envres.2020.110265","article-title":"SARS-CoV-2 coronavirus in water and wastewater: A critical review about presence and concern","volume":"193","author":"Tran","year":"2021","journal-title":"Environ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111999","DOI":"10.1016\/j.jphotobiol.2020.111999","article-title":"Light-based technologies for management of COVID-19 pandemic crisis","volume":"212","author":"Sabino","year":"2020","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"093001","DOI":"10.1088\/1612-202X\/abab14","article-title":"Photoinactivation of coronaviruses: Going along the optical spectrum","volume":"17","author":"Strakhovskaya","year":"2020","journal-title":"Laser Phys. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/vox.12888","article-title":"Inactivation of three emerging viruses-severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus-in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light","volume":"115","author":"Eickmann","year":"2020","journal-title":"Vox Sang."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102112","DOI":"10.1016\/j.pdpdt.2020.102112","article-title":"Antiviral Photodynamic Therapy: Inactivation and Inhibition of SARS-CoV-2 In Vitro Using Methylene Blue and Radahlorin","volume":"33","author":"Svyatchenko","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106202","DOI":"10.1016\/j.ijantimicag.2020.106202","article-title":"Methylene blue inhibits replication of SARS-CoV-2 in vitro","volume":"56","author":"Gendrot","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/1011-1344(95)07148-2","article-title":"Photoinactivation of bacteria. Use of a cationic water-soluble zinc phthalocyanine to photoinactivate both gram-negative and gram-positive bacteria","volume":"32","author":"Minnock","year":"1996","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1039\/b202031a","article-title":"Photophysical, photochemical and antibacterial photosensitizing properties of a novel octacationic Zn(II)-phthalocyanine","volume":"1","author":"Segalla","year":"2002","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_15","unstructured":"Kuznetsova, N., Kaliya, O., Strakhovskaya, M., and Zubairov, M. (2009, January 14\u201315). Photodynamic inactivation of avian influenza virus in aqueous media. Proceedings of the First International Workshop on Application of Redox Technologies in the Environment, Istanbul, Turkey."},{"key":"ref_16","first-page":"1305","article-title":"Electrostatic binding of substituted metal phthalocyanines to enterobacterial cells: Its role in photodynamic inactivation","volume":"74","author":"Strakhovskaya","year":"2009","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1016\/j.ejmech.2010.01.058","article-title":"Photodynamic inactivation of Escherichia coli and Streptococcus mitis by cationic zinc(II) phthalocyanines in media with blood derivatives","volume":"45","author":"Spesia","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ejmech.2014.07.022","article-title":"Photodynamic inactivation of bacteria and viruses using two monosubstituted zinc(II) phthalocyanines","volume":"84","author":"Ke","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1016\/j.bmcl.2015.04.004","article-title":"Highly positive-charged zinc(II) phthalocyanine as non-aggregated and efficient antifungal photosensitizer","volume":"25","author":"Li","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Korneev, D., Kurskaya, O., Sharshov, K., Eastwood, J., and Strakhovskaya, M. (2019). Ultrastructural Aspects of Photodynamic Inactivation of Highly Pathogenic Avian H5N8 Influenza Virus. Viruses, 11.","DOI":"10.3390\/v11100955"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1142\/S1088424607000680","article-title":"Cationic Zn and Al phthalocyanines: Synthesis, spectroscopy and photosensitizing properties","volume":"11","author":"Makarov","year":"2007","journal-title":"J. Porphyr. Phthalocyanines"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/ppl.12570","article-title":"Multiparticle Brownian dynamics simulation of experimental kinetics of cytochrome bf oxidation and photosystem 1 reduction by plastocyanin","volume":"161","author":"Kovalenko","year":"2017","journal-title":"Physiol. Plant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/ppl.12940","article-title":"Comparative analysis of plastocyanin-cytochrome f complex formation in higher plants, green algae and cyanobacteria","volume":"166","author":"Fedorov","year":"2019","journal-title":"Physiol. Plant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7128","DOI":"10.1021\/acs.jpcb.0c04553","article-title":"Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane","volume":"124","author":"Woo","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1021\/acs.jpcb.7b11707","article-title":"Molecular Mechanism of Uptake of Cationic Photoantimicrobial Phthalocyanine across Bacterial Membranes Revealed by Molecular Dynamics Simulations","volume":"122","author":"Orekhov","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/jmr.577","article-title":"The Poisson-Boltzmann equation for biomolecular electrostatics: A tool for structural biology","volume":"15","author":"Fogolari","year":"2002","journal-title":"J. Mol. Recognit."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1134\/S1607672916030066","article-title":"The role of electrostatic interactions in the process of diffusional encounter and docking of electron transport proteins","volume":"468","author":"Kovalenko","year":"2016","journal-title":"Doklady Biochem. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1134\/S0006350915040156","article-title":"The identification of intermediate states of the electron-transfer proteins plastocyanin and cytochrome f diffusional encounters","volume":"60","author":"Khruschev","year":"2015","journal-title":"Biophysics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.1073\/pnas.93.15.7446","article-title":"Photo-induced inactivation of viruses: Adsorption of methylene blue, thionine, and thiopyronine on Qbeta bacteriophage","volume":"93","author":"Jockusch","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104719","DOI":"10.1016\/j.micpath.2020.104719","article-title":"Spike glycoproteins: Their significance for corona viruses and receptor binding activities for pathogenesis and viral survival","volume":"150","author":"Noman","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"342","DOI":"10.20411\/pai.v5i1.377","article-title":"The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET","volume":"5","author":"Thomas","year":"2020","journal-title":"Pathog. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Vigant, F., Lee, J., Hollmann, A., Tanner, L.B., Akyol Ataman, Z., Yun, T., Shui, G., Aguilar, H.C., Zhang, D., and Meriwether, D. (2013). A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003297"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Calligari, P., Bobone, S., Ricci, G., and Bocedi, A. (2020). Molecular Investigation of SARS\u2013CoV-2 Proteins and Their Interactions with Antiviral Drugs. Viruses, 12.","DOI":"10.3390\/v12040445"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3322\/caac.20114","article-title":"Photodynamic therapy of cancer: An update","volume":"61","author":"Agostinis","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1751-1097.1991.tb03669.x","article-title":"The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen","volume":"53","author":"Moan","year":"1991","journal-title":"Photochem. Photobiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Almeida, A., Faustino, M.A.F., and Neves, M.G.P.M.S. (2020). Antimicrobial Photodynamic Therapy in the Control of COVID-19. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060320"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"600372","DOI":"10.3389\/fphar.2020.600372","article-title":"Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19","volume":"11","author":"Bojadzic","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_39","first-page":"123","article-title":"Virus inactivation under the photodynamic effect of phthalocyanine zinc(II) complexes","volume":"72","author":"Remichkova","year":"2017","journal-title":"Z. Nat. C"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/4\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:59:09Z","timestamp":1760363949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/4\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,9]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["v13040643"],"URL":"https:\/\/doi.org\/10.3390\/v13040643","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,9]]}}}