In Vitro Virucidal Effect of Intranasally Delivered Chlorpheniramine Maleate Compound Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Abstract

Abstract Background. The initial global outbreak of the novel coronavirus disease 2019 (COVID-2019) pandemic, responsible for the severe acute respiratory syndrome 2 (SARS-CoV-2), was first reported in Wuhan, China, at the end of December 2019. COVID-19 shares similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and it 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 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 chlorpheniramine maleate (CPM) in a nasal spray composition currently in development as an anti-allergy medication.Methods. The virucidal activity of chlorpheniramine maleate was tested using viral stock of SARS-CoV-2, USA-WA1/2020 strain in Vero 76 infected cells. The end-point titer (CCID50) values were calculated with 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 by one-way ANOVA 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 CCID50 per 0.1 mL, a statistically significant reduction of 2.5 log10 CCID50.Conclusions. This study demonstrates the strong virucidal effect against SARS-CoV-2 of a nasal spray containing chlorpheniramine maleate. Given that CPM has broad antiviral effects against influenza, virucidal effect against SARS-CoV-2, and coadjuvant effects with hydroxychloroquine in treating multidrug-resistant malaria with minimal side effects. 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 chloroquine alone, in hospitalized patients with SARS-CoV-2.