Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

• Main Authors: Villoutreix BO, Krishnamoorthy R, Tamouza R, Leboyer M, Beaune P
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-04-01
• Series: Advances and Applications in Bioinformatics and Chemistry
• Subjects: chemoinformatics; covid-19; high-throughput screening; phenothiazine; prophylaxis; antihistamine; drug repurposing
• Online Access: https://www.dovepress.com/chemoinformatic-analysis-of-psychotropic-and-antihistaminic-drugs-in-t-peer-reviewed-article-AABC

Bruno O Villoutreix,1 Rajagopal Krishnamoorthy,2 Ryad Tamouza,2 Marion Leboyer,2 Philippe Beaune3 1INSERM U1141, NeuroDiderot, Université de Paris, Hôpital Robert-Debré, Paris, F-75019, France; 2Université Paris Est Créteil, INSERM U955, IMRB, Laboratoire Neuropsychiatrie Translationnelle, AP-HP, Département Medico-Universitaire de Psychiatrie et d’Addictologie (DMU ADAPT), Hôpital Henri Mondor, Fondation FondaMental, Créteil, F-94010, France; 3INSERM U1138, Centre de Recherche des Cordeliers, Université de Paris, Paris, 75006, FranceCorrespondence: Bruno O Villoutreix Email [e-mail]: There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients.Objective: Based upon clinical observations, we proposed that some psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection. This observation is investigated in the light of experimental in vitro data on SARS-CoV-2.Methods: SARS-CoV-2 high-throughput screening results are available at the NCATS COVID-19 portal. We investigated the in vitro anti-viral activity of many psychotropic and antihistaminic drugs using chemoinformatics approaches.Results and Discussion: We analyze our clinical observations in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could be used as prophylactic drugs. Other cationic amphiphilic drugs used in other disease areas are also highlighted. Recent analyses of patient electronic health records reported by several research groups indicate that some of these molecules could be of interest at different stages of the disease progression. In addition, recently reported drug combination studies further suggest that it might be valuable to associate several cationic amphiphilic drugs. Taken together, these observations underline the need for clinical trials to fully evaluate the potentials of these molecules, some fitting in the so-called category of broad-spectrum antiviral agents. Repositioning orally available drugs that have moderate side effects and should act on molecular mechanisms less prone to drug resistance would indeed be of utmost importance to deal with COVID-19.Keywords: chemoinformatics, COVID-19, high-throughput screening, phenothiazine, prophylaxis, antihistamine, drug repurposing