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

Ana-Maria Udrea; Speranta Avram; Simona Nistorescu; Mihail-Lucian Pascu; Mihaela Oana Romanitan

doi:10.1016/j.jphotobiol.2020.111997

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

J Photochem Photobiol B. 2020 Oct:211:111997. doi: 10.1016/j.jphotobiol.2020.111997. Epub 2020 Aug 15.

Authors

Ana-Maria Udrea¹, Speranta Avram², Simona Nistorescu³, Mihail-Lucian Pascu⁴, Mihaela Oana Romanitan⁵

Affiliations

¹ Laser Department, National Institute for Laser, Plasma and Radiation Physics, Magurele, Ilfov, Romania; Department of Anatomy, Animal Biology, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
² Department of Anatomy, Animal Biology, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
³ Laser Department, National Institute for Laser, Plasma and Radiation Physics, Magurele, Ilfov, Romania; Department of Botany and Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania.
⁴ Laser Department, National Institute for Laser, Plasma and Radiation Physics, Magurele, Ilfov, Romania; Faculty of Physics, University of Bucharest, Magurele, Romania. Electronic address: mihai.pascu@inflpr.ro.
⁵ Stockholm South General Hospital, Department of Emergency internal medicine and Neurology, Karolinska Institute Stroke Research Network at Södersjukhuset, 118 83 Stockholm, Sweden.

Abstract

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 (M^pro) 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 M^pro. 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.

Keywords: COVID-19; Laser irradiated phenothiazines; Molecular docking; SARS-CoV-2.

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Antiviral Agents / radiation effects
Betacoronavirus* / drug effects
Betacoronavirus* / enzymology
COVID-19
COVID-19 Drug Treatment
Coronavirus 3C Proteases
Coronavirus Infections / drug therapy*
Coronavirus Infections / epidemiology
Coronavirus Infections / virology
Cysteine Endopeptidases / chemistry
Host Microbial Interactions / drug effects
Humans
Lasers, Solid-State
Molecular Docking Simulation
Pandemics
Phenothiazines / chemistry
Phenothiazines / pharmacology*
Phenothiazines / radiation effects
Photochemical Processes
Pneumonia, Viral / drug therapy*
Pneumonia, Viral / epidemiology
Pneumonia, Viral / virology
SARS-CoV-2
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors
Viral Nonstructural Proteins / chemistry

Substances

Antiviral Agents
Phenothiazines
Viral Nonstructural Proteins
Cysteine Endopeptidases
Coronavirus 3C Proteases