Laser irradiated phenothiazines: New potential treatment for COVID-19 explored by molecular docking

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 211; p. 111997
• Main Authors: Udrea, Ana-Maria, Avram, Speranta, Nistorescu, Simona, Pascu, Mihail-Lucian, Romanitan, Mihaela Oana
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.10.2020; Elsevier BV
• Subjects: Affinity; Animal models; Antihistamines; Antipsychotics; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - radiation effects; Betacoronavirus - drug effects; Betacoronavirus - enzymology; Binding; bioactive properties; Biological activity; Coronavirus 3C Proteases; Coronavirus Infections - drug therapy; Coronavirus Infections - epidemiology; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 Drug Treatment; COVID-19 infection; Cysteine Endopeptidases - chemistry; Host Microbial Interactions - drug effects; Humans; Irradiation; Laser beams; Laser irradiated phenothiazines; Lasers, Solid-State; markets; Molecular docking; Molecular Docking Simulation; Neodymium lasers; Pandemics; Phenothiazines; Phenothiazines - chemistry; Phenothiazines - pharmacology; Phenothiazines - radiation effects; photobiology; Photochemical Processes; photochemistry; Pneumonia, Viral - drug therapy; Pneumonia, Viral - epidemiology; Pneumonia, Viral - virology; proteinases; Psychotropic drugs; SARS-CoV-2; Semiconductor lasers; Severe acute respiratory syndrome coronavirus 2; Structure-Activity Relationship; Thioridazine; Viral diseases; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - chemistry; Viruses; YAG lasers; COVID-19; SARS-CoV-2; Laser irradiated phenothiazines; Molecular docking
• ISSN: 1011-1344; 1873-2682; 1873-2682
• DOI: 10.1016/j.jphotobiol.2020.111997

The worldwide infection with the new Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) demands urgently new potent treatment(s). In this study we predict, using molecular docking, the binding affinity of 15 phenothiazines (antihistaminic and antipsychotic drugs) when interacting with the main protease (Mpro) of SARS-CoV-2. Additionally, we tested the binding affinity of photoproducts identified after irradiation of phenothiazines with Nd:YAG laser beam at 266 nm respectively 355 nm. Our results reveal that thioridazine and its identified photoproducts (mesoridazine and sulforidazine) have high biological activity on the virus Mpro. This shows that thioridazine and its two photoproducts might represent new potent medicines to be used for treatment in this outbreak. Such results recommend these medicines for further tests on cell cultures infected with SARS-CoV-2 or animal model. The transition to human subjects of the suggested treatment will be smooth due to the fact that the drugs are already available on the market. [Display omitted] •Binding affinity of 15 phenothiazines with the main protease (Mpro) of SARS-CoV-2 is predicted by molecular docking.•We test the binding affinity of photoproducts identified after irradiation of phenothiazines with Nd:YAG laser beam.•Thioridazine and its photoproducts, mesoridazine and sulforidazine, have high biological activity on the virus Mpro.•Results recommend these medicines for further tests on cell cultures infected with SARS-CoV-2 or animal model.