Background The initial global outbreak of the novel coronavirus disease 2019 (COVID-2019) pandemic, which is responsible for the severe acute respiratory syndrome 2 (SARS-CoV-2), shares similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) and behaves similarly to influenza with a high intranasal viral load. The genome sequence of COVID-19 opened the opportunity for multiple in vitro and clinical trials, but we still do not have a clear path to treatment. Chlorpheniramine maleate (CPM) is a safe and effective antihistamine with potent antiviral activity against various strains of influenza A/B, thus suggesting that CPM has broad antiviral activity. We tested the virucidal potential of CPM in a nasal spray composition currently in development as an anti-allergy medication. Methods The virucidal activity of CPM was tested using viral stock of SARS-CoV-2, USA-WA1/2020 strain in Vero 76 infected cells. The endpoint titer 50% cell culture infection dose (CCID 50 ) values were calculated using the Reed-Muench (1948) equation. Three independent replicates of each sample were tested, and the average and standard deviation were calculated. Results were compared with untreated controls using one-way ANOVA (analysis of variance) with Dunnett’s multiple comparison test in GraphPad Prism (version 8) software. Results After 25 minutes of contact time, the nasal spray reduced the levels of the virus from 4.2 to 1.7 log10 CCID 50 per 0.1 mL, a statistically significant 2.5 log reduction value or 99.7% reduction in the viral load. Conclusions This study demonstrates the strong virucidal effect against SARS-CoV-2 of a nasal spray containing CPM. Given that CPM has broad antiviral effects against influenza and virucidal effect against SARS-CoV-2, we propose two further studies: a randomized placebo-controlled study of intranasally delivered chlorpheniramine in patients with mild-to-moderate SARS-CoV-2 and a second study aiming to determine the potential antiviral and adjuvant effects of CPM plus hydroxychloroquine, versus hydroxychloroquine alone, in hospitalized patients with SARS-CoV-2.

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