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

Objective: We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.

Methods: Open high-throughput screening results are now available at the NCATS COVID-19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.

Results and Discussion: We here revisit our initial hypothesis 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 eventually be used as prophylactic drugs. Further, recent analyses of electronic health records reported by several research groups, including drug combinations, indicate that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these potential small molecules broad-spectrum antiviral agents. Orally available drugs would indeed be of outmost importance to deal with COVID-19.