In Vitro Virucidal Effect of Intranasally Delivered Chlorpheniramine Maleate Compound Against Severe Acute Respiratory Syndrome Coronavirus 2

Abstract

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.

Inhalation monoclonal antibody therapy: a new way to treat and manage respiratory infections

“…Second, most of the medications that treat respiratory diseases work in the organs of the respiratory system rather than in the periphery (Labiris and Dolovich 2003 ). The development of nasal spray treatments for SARS-CoV-2 is underway, and early clinical studies have confirmed that this approach is safe and can be used to prevent respiratory spread of SARS-CoV-2 (Westover et al 2020 ; Zhang et al 2020 ). Inhaled antibodies have the potential to be employed as a treatment, particularly for individuals who are not hospitalised and have a lower pathogen load.…”

Antihistamine and cationic amphiphilic drugs, old molecules as new tools against the COVID-19?

“…Many antihistamine drugs are also CAD and as such could act on virus entry while, also exerting a negative regulation on IL-6 release from human lung macrophages which are secreted in great amounts during the cytokine-storm of COVID-19 [ 10 , 11 ]. The most recent data indicate that antihistamines (anti-H 1 ) medications in general and particularly phenothiazines and derivates could be a useful strategy against SARS-CoV-2 at multiple stages, from prophylaxis to preventing complications of the infection itself [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ]. Moreover, in a large sample of 219,000 electronic health records, 3 antihistamine medications (azelastine, diphenhydramine and hydroxyzine) were associated with reduced incidence of SARS-CoV-2 in subjects above the age of 61 [ 17 ],.…”

Chlorpheniramine maleate nasal spray in COVID-19 patients: Case Series

“…A study conducted on SARS-cov-2 stock to highlight the virucidal potential of CPM showed a reduction of 99.7% in viral load in Vero 76 infected cells. [7] Mostafa et al in a study on FDA approved drugs that have potent antiviral activity against SARS-CoV-2 concluded that besides antimicrobial drugs like Azithromycin, Niclosamide, and Nitazoxanide, several antihistamines and anti-inflammatory drugs could reduce SARS-CoV-2 replication in vitro. Of these, Chlorpheniramine maleate, a competitive histamine H1 receptor antagonist, exhibited strong virucidal activity against a broad spectrum of influenza viruses.…”