In Vitro Analysis of the Anti-viral Potential of nasal spray constituents against SARS-CoV-2 (original) (raw)

The effects of ethyl lauroyl arginine hydrochloride (ELAH) in nasal spray formula on SARS-Cov-2

2021

SARS-CoV-2 and coronaviruses, enveloped RNA viruses, are major causes of acute human respiratory diseases. The aim of the study was to investigate the broad-spectrum antiviral effects of ethyl lauroyl arginine hydrochloride (ELAH) in in vitro and in vivo assays. Cell-based assays found that the pseudovirus VSV-SARS-CoV-2 was inhibited with an EC50 of 15 micrograms/ml, with complete inhibition achieved at 110 micrograms/ml. The effects were comparable to those observed with anti-SARS-CoV-2 antibody neutralization assays against VSV-SARS-CoV-2. Intranasal administration of the Wuhan strain of SARS-CoV-2 treated in vitro with ELAH inhibited the disease symptoms caused by the virus in a Syrian hamster model compared to that caused by the same dose of virus treated in vitro with medium alone. Subgenomic RNA and total RNA viral load were concomitantly reduced in the treated animals compared with the control group. In cell-based studies, pretreatment of susceptible cells with 1–10 microgra...

In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray

Australian Journal of Otolaryngology

Background: Nasal disinfection with 0.5% povidone-iodine (PVP-I) may be a useful adjunct in the management of COVID-19. The purpose of this article is to confirm the in vitro activity of the PVP-I nasal spray against SARS-CoV-2 and whether that may translate into reduced nasal shedding in vivo. Methods: Two SARS-CoV-2 virus isolates were exposed to 0.5% PVP-nasal spray (Nasodine®) for different times in vitro, with PCR and cell culture used to assess impact on viral infectivity and RNA copies. An open label in vivo single arm pilot study of 14 subjects with positive COVID-19 PCR diagnosis was undertaken. Baseline nasal swabs were collected to quantify SARS-CoV-2 pre-treatment, followed by a single 0.5% PVP nasal spray application (1.12 mL). Nasal swabs were collected at 5, 15, and 60 minutes post-dose to assess immediate and residual impact of treatment. Results: In vitro, the nasal spray reduced infectivity by 3.5 log10 TCID 50 /mL (99.97%) after 15 seconds exposure and eliminated detectable viral infectivity after 60 seconds; there was no effect on viral RNA detection by PCR. In vivo, culturable virus (VOC beta/B.1.351 variant) was obtained from 6 of 14 PCRconfirmed positive subjects; in these subjects, 5 minutes after the single PVP-I dose, the mean viral titre was reduced by 65% versus baseline and by 79% versus baseline at 60 minutes post-dose. 5 of the 6 subjects (83%), had reduction or cessation of viral shedding at 5 minutes in all 6 subjects, virus titers 60 minutes post-dose were below baseline value. 0.5% PVP-I treatment didn't interfere with the laboratory diagnosis of COVID-19 via PCR-detection of viral RNA in humans. Conclusions: 0.5% PVP-I nasal spray is rapidly virucidal to SARS-CoV-2 in vitro using exposure times consistent with nasal residence; single in vivo nasal administration reduced infectious viral titers in COVID-19 subjects with culturable virus. A single application of 0.5% PVP-I nasal spray does not interfere with PCR-mediated laboratory diagnosis of COVID-19. We are undertaking a large double blinded randomized controlled trial to confirm if repeated application of 0.5% PVP-I nasal spray over a longer period could be useful in suppressing viral shedding and transmission risk in COVID-positive patients.

Drug-Free Nasal Spray as a Barrier against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia

International Journal of Molecular Sciences

The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after inf...

Drug-free nasal spray as a barrier against SARS-CoV-2 infection: safety and efficacy in human nasal airway epithelia

2021

BackgroundFor SARS-CoV-2 and other respiratory viruses, the nasal epithelium is a key portal for infection. Therefore, the nose is an important target of prophylactic and therapeutic interventions against these viruses. We developed a nasal spray (AM-301, a medical device marketed as Bentrio) to protect against infection by SARS-CoV-2 and potentially other viruses.Aims of the studyTo test the safety and efficacy of AM-301 against SARS-CoV-2 infection.MethodsAM-301 was tested on an in vitro 3D model of primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in prophylaxis and infection mitigation assays.ResultsAM-301 did not have any detrimental effect on the nasal epithelium. Prophylactic treatment with AM-301 reduced viral titer significantly vs. controls over 4 days, reaching a maximum reduction of 99%. When treatment with AM-301 was started 24 o...

Iota-carrageenan and Xylitol inhibit SARS-CoV-2 in cell culture

COVID-19 (coronavirus disease 2019) is a pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affecting millions of persons around the world. There is an urgent unmet need to provide an easy-to-produce, affordable medicine to prevent transmission and provide early treatment for this disease. The nasal cavity and the rhinopharynx are the sites of initial replication of SARS-CoV-2. Therefore, a nasal spray may be a suitable dosage form for this purpose. The main objective of our study was to test the antiviral action of three candidate nasal spray formulations against SARS-CoV-2. We have found that iota-carrageenan in concentrations as low as 6 µg/ mL inhibits SARS-CoV-2 infection in Vero cell cultures. The concentrations found to be active in vitro against SARS-CoV-2 may be easily achieved by the application of nasal sprays already marketed in several countries. Xylitol at a concentration of 5 % m/V has proved to be viricidal on its own and the as...

A novel antiviral formulation inhibits SARS-CoV-2 infection of human bronchial epithelium

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of in vitro cellular toxicity was detected in ViruSAL treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together t...

Nasal sprays for treating COVID-19: a scientific note

Pharmacological Reports

Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate responses and cell-mediated systemic immunity, including serum antibodies, have been the primary focus of practically all studies of the immune response to COVID-19. However, owing to the difficulties encountered by the conventional route, alternative routes for prophylaxis and therapy became the need of the hour. The first site invaded by SARS-CoV-2 is the upper respiratory tract. Nasal vaccines are already in different stages of development. Apart from prophylactic purposes, mucosal immunity can be exploited for therapeutic purposes too. The nasal route for drug delivery offers many advantages over the conventional route. Besides offering a needle-free delivery, they can be selfadministered. They present less logistical burden as there is no need for refrigeration. The present article focuses on various aspects of nasal spray for eliminating COVID-19. Keywords SARS-CoV-2 • Immunity • Nasal route • Nasal vaccine • Nasal spray • Clinical trials • Devices Abbreviations ACE2 Angiotensin converting enzyme 2 CD4 Clusters of differentiation 4 cGMP Guanosine mono phosphate COVID-19 Coronavirus disease-2019 HCoV Human coronavirus HPMC Hydroxypropyl methyl cellulose IgG Immunoglobulin G IL-2 Interleukin-2 MERS-CoV Middle East respiratory syndrome coronavirus mRNA Messenger ribonucleic acid NC Nasal cycle NONS Nitric oxide nasal spray RNA Ribonucleic acid SARS-CoV-2 Severe acute respiratory syndrome coronavirus disease 2 URTI Upper respiratory tract infection

A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx

We studied the virucidal efficacy of 0.4% povidone-iodine (PVP-I) nasal spray against SARS-CoV-2 in the patients’ nasopharynx at 3 minutes and 4 hours after PVP-I exposure. We used an open-label, before and after design, single arm pilot study of adult patients with RT-PCR-confirmed COVID-19 within 24 hours. All patients received three puffs of 0.4% PVP-I nasal spray in each nostril. Nasopharyngeal (NP) swabs were collected before the PVP-I spray (baseline, left NP samples), and at 3 minutes (left and right NP samples) and 4 hours post-PVP-I spray (right NP samples). All swabs were coded to blind assessors and transported to diagnostic laboratory and tested by RT-PCR and cultured to measure the viable SARS-CoV-2 within 24 hours after collection. Fourteen patients were enrolled but viable SARS-CoV-2 was cultured from 12 patients (85.7%). The median viral titer at baseline was 3.5 log TCID50/mL (IQR 2.8-4.0 log TCID50/mL). At 3 minutes post-PVP-I spray via the left nostril, viral tite...

Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2

Journal of Dental Research

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has ...