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

Mapping Intimacies ◽

10.21203/rs.3.rs-25854/v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Gustavo Ferrer ◽

Jonna Westover

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Antiviral Activity ◽

Nasal Spray ◽

Influenza A ◽

Multidrug Resistant ◽

Controlled Study ◽

Chlorpheniramine Maleate ◽

Viral Stock ◽

Virucidal Effect

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.

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

Cureus ◽

10.7759/cureus.10501 ◽

2020 ◽

Author(s):

Jonna B Westover ◽

Gustavo Ferrer ◽

Hector Vazquez ◽

Arian Bethencourt-Mirabal ◽

Camille Celeste Go

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Chlorpheniramine Maleate ◽

Virucidal Effect

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Antiviral activity of lambda-carrageenan against influenza viruses in mice and severe acute respiratory syndrome coronavirus 2 in vitro

10.1101/2020.08.23.255364 ◽

2020 ◽

Author(s):

Yejin Jang ◽

Heegwon Shin ◽

Myoung Kyu Lee ◽

Oh Seung Kwon ◽

Jin Soo Shin ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Antiviral Activity ◽

Influenza A ◽

Antiviral Agent ◽

Influenza Viruses ◽

Host Cells ◽

Progeny Virus ◽

Dependent Manner ◽

Viral Attachment

ABSTRACTInfluenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with EC50 values ranging from 0.3–1.4 μg/ml. No toxicity to host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing entry. Moreover, intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection by several respiratory viruses.

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Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo

Frontiers in Microbiology ◽

10.3389/fmicb.2014.00171 ◽

2014 ◽

Vol 5 ◽

Cited By ~ 12

Author(s):

Emanuel Haasbach ◽

Carmen Hartmayer ◽

Alice Hettler ◽

Alicja Sarnecka ◽

Ulrich Wulle ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Black Currant

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In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection

Journal of Ethnopharmacology ◽

10.1016/j.jep.2016.03.020 ◽

2016 ◽

Vol 185 ◽

pp. 327-340 ◽

Cited By ~ 15

Author(s):

Amin Haghani ◽

Parvaneh Mehrbod ◽

Nikoo Safi ◽

Nur Ain Aminuddin ◽

Azadeh Bahadoran ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Edible Bird’S Nest

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Antiviral Activity of Benzoic Acid Derivative NC-5 Against Influenza A Virus and Its Neuraminidase Inhibition

International Journal of Molecular Sciences ◽

10.3390/ijms20246261 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6261

Author(s):

Min Guo ◽

Jiawei Ni ◽

Jie Yu ◽

Jing Jin ◽

Lingman Ma ◽

...

Keyword(s):

Antiviral Activity ◽

Benzoic Acid ◽

Influenza A Virus ◽

Influenza A ◽

Matrix Protein ◽

Influenza Viruses ◽

Drug Candidate ◽

Dependent Manner ◽

Drug Resistant

The currently available drugs against influenza A virus primarily target neuraminidase (NA) or the matrix protein 2 (M2) ion channel. The emergence of drug-resistant viruses requires the development of new antiviral chemicals. Our study applied a cell-based approach to evaluate the antiviral activity of a series of newly synthesized benzoic acid derivatives, and 4-(2,2-Bis(hydroxymethyl)-5-oxopyrrolidin-l-yl)-3-(5-cyclohexyl-4H-1,2,4-triazol-3-yl)amino). benzoic acid, termed NC-5, was found to possess antiviral activity. NC-5 inhibited influenza A viruses A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) in a dose-dependent manner. The 50% effective concentrations (EC50) for H1N1 and H1N1-H275Y were 33.6 μM and 32.8 μM, respectively, which showed that NC-5 had a great advantage over oseltamivir in drug-resistant virus infections. The 50% cytotoxic concentration (CC50) of NC-5 was greater than 640 μM. Orally administered NC-5 protected mice infected with H1N1 and H1N1-H275Y, conferring 80% and 60% survival at 100 mg/kg/d, reducing body weight loss, and alleviating virus-induced lung injury. NC-5 could suppress NP and M1 protein expression levels during the late stages of viral biosynthesis and inhibit NA activity, which may influence virus release. Our study proved that NC-5 has potent anti-influenza activity in vivo and in vitro, meaning that it could be regarded as a promising drug candidate to treat infection with influenza viruses, including oseltamivir-resistant viruses.

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#Nitrosocarbonyls 1: Antiviral Activity ofN-(4-Hydroxycyclohex-2-en-1-yl)quinoline-2-carboxamide against the Influenza A Virus H1N1

The Scientific World JOURNAL ◽

10.1155/2014/472373 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Dalya Al-Saad ◽

Misal Giuseppe Memeo ◽

Paolo Quadrelli

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Small Molecules ◽

Influenza A ◽

Nucleoside Analogues ◽

Virus H1n1 ◽

Antiviral Activities ◽

Synthetic Approaches ◽

Carbocyclic Nucleoside

Influenza virus flu A H1N1 still remains a target for its inhibition with small molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic approaches is presented along with thein vitroantiviral tests. The nucleoside derivatives were tested for their inhibitory activity against a variety of viruses. Promising antiviral activities were found for specific compounds in the case of flu A H1N1.

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