Chemoreactome screening of pharmaceutical effects on SARS-CoV-2 and human virome to help decide on drug-based COVID-19 therapy

Abstract

Background. So-called rational drug design is suboptimal when it comes to finding effective and safe drug-based treatment for COVID-19. Another approach seems promising: to reprofile the pharmaceuticals registered in the Anatomical, Therapeutic, and Chemical Classifier (ATC).Material and methods. Chemoreactome screening, a method that simulates the results of inhibiting viral growth in a cell culture, models the effects of pharmaceuticals on the human virome, and estimates the adverse effects of medicines, was used to reprofile about 2700 pharmaceuticals from the ATC. The information technology behind chemoreactome analysis is based on the topological recognition theory advanced by the Institute of Pharmaceutical Informatics, Federal Research Center for Informatics and Control, Russian Academy of Sciences.Results. Sixty two pharmaceuticals and 20 micronutrients were found to have a pronounced antiviral effect with minimal side effects. Comparison against data of basic research and clinical trials showed 31 out of 62 pharmaceuticals to have been independently confirmed usable in COVID-19 treatment. These inhibit coronaviral proteins and/or function as adaptogenic molecules that improve the functioning of cells exposed to viral stress. Glucosamine sulfate was found to have the best safety profile and minimum effects on the healthy human virome out of all the tested anticoronaviral micronutrients.Conclusions. Reprofiling of pharmaceuticals registered in the ATC could significantly speed up the search for more effective and safer drugbased COVID-19 treatments. Several micronutrients show promise for long-term coronavirus prevention, especially in the elderly.