Pharmacovigilance-based drug repurposing: The search for inverse signals via OpenVigil identifies putative drugs against viral respiratory infections.

AIM: Pharmacovigilance data are primarily used to identify adverse drug reactions by screening for disproportionate reporting, i.e. more reports of certain combinations of adverse events and drugs than expected. However, scanning for associations of drugs and adverse events that occur less frequently than expected provides hypotheses for drug repurposing, i.e. a known drug could be therapeutically beneficial for a new indication like the coronavirus disease (COVID-19). As coronavirus related adverse events are scarce in pharmacovigilance data prior to 2020, we searched for drugs suitable against similar viral diseases. METHODS: In this observational, retrospective, pharmacovigilance study, drugs associated with viral respiratory tract infections and/or diseases caused by RNA-viruses, which are phylogenetically similar to SARS-CoV-2, were extracted from the U.S. FAERS pharmacovigilance data 2004Q1 to 2020Q2 using OpenVigil 2.1-MedDRA17, filtered for significant inverse associations (ROR<1 and padj <0.05), checked for implausibility (e.g., only topically) or clinical infeasibility (e.g., strong cytotoxic effects), and categorised by their WHO Anatomical Therapeutic Chemical (ATC) classification code. RESULTS: A total of 126 drugs were identified. ATC clustering of the manually curated list of 112 candidate drugs revealed female sex hormones, anti-diabetics, neuropharmacological sigma-receptor modulators, peptidase inhibitors, antiviral drugs, nicotinic acetylcholine receptor agonists, and tyrosine kinase inhibitors as putatively antiviral. CONCLUSION: Scanning for inverse signals in pharmacovigilance data provides new hypotheses for drug repurposing, theoretically for all indications. Concerning the treatment of viral respiratory infections, there is affirmative data for some candidate drugs; the remaining proposed candidate drugs without already known antiviral mechanism of action should stimulate further exploration.