Nasal sprays for treating COVID-19: a scientific note (original) (raw)
Related papers
PLOS Pathogens, 2021
Recent reports of the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by fully vaccinated people [1] do not undermine the value of injected vaccines that continue to protect against serious illness and hospitalisation. They are, however, an early warning for immediate action to develop new drugs and approaches against Coronavirus Disease 2019 (COVID-19). The logical answer is to target the initial nasal portal of COVID-19 entry into the body with prophylactic drugs, which, together with injected vaccines, could potentially completely prevent infection and subsequent transmission of a range of variants. This paper outlines published work in this vital area in the hope that it becomes an urgent priority for development. COVID-19 variants Over 12,000 mutations have been catalogued in SARS-CoV-2 genomes [2] and have resulted in new SARS-CoV-2 variants, including those identified in South Africa (B.1.351), United Kingdom (B.1.1.7), California (B.1.427 and B.1.429), Brazil (P.1 and P.2), India (B1.617.2 = Delta), Peru (C.37 = Lambda), and Colombia (Mu). Such variants may have increased transmissibility and pathogenicity, higher viral loads, and vaccine resistance [3-5]. A missed opportunity Vaccines provide short-term relief from COVID-19, but rapid evolution of resistant viral variants necessitates additional supportive strategies, including broad-spectrum antiviral agents coupled with innovative prophylactic and therapeutic processes. Antiviral agents against SARS-CoV-2 should have been repurposed drugs, but of all the drugs tested, those effective in the later stages of infection, such as dexamethasone, are the main ones granted approval for emergency use [6]. One exception has been monoclonal antibody therapy [7]. An important missing link has been the lack of innovative drug development for treating the early stages of COVID-19 infection. Disease pathology extols studying the initial interactions of invading pathogens with the body, involving adsorption, colonisation, penetration, multiplication, and host innate immunity [8].
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...
ABSTRACTSuccessful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP™) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP™ exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any dete...
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.
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...
A Review on Modern Use of Intranasal Vaccination in the Treatment of SARS-COV-2
2021
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for efficient SARS coronavirus 2 (SARS-CoV-2) preventative vaccines to limit the burden and spread of SARS-CoV-2 in humans. Intranasal immunization is a promising technique for preventing COVID-19 because the nasal mucosa acts as a first line of defense against SARS-CoV-2 entrance before the virus spreads to the lungs. Nasal vaccination has many advantages over traditional vaccine administration methods. These include the simplicity of administration without the use of needles, which decreases the risks of needle stick injuries and disposal. This channel also provides simple access to a crucial portion of the immune system that can stimulate other mucosal sites throughout the body. By targeting immunoglobulin A (IgA), antibodies found only in the mucosa, an intranasal vaccination would elicit immunological responses in the nose, throat, and lungs. Potential pathogens are trapped by the mucosa, which act...
In Vitro Analysis of the Anti-viral Potential of nasal spray constituents against SARS-CoV-2
Viral pandemics have taken a significant toll on humanity and the world now is contending with the SARS-CoV-2 epidemic. Readily available economical preventive measures should be immediately explored. Xylitol has been reported to reduce the severity of viral infections as well as the severity of pneumonia, and increase the survivability of animal subjects. Since pneumonia and acute respiratory distress syndrome are potentially fatal complications of COVID-19, the present study tested the in vitro effectiveness of xylitol against SARS-CoV-2. Virus titers and LRV of SARS-CoV-2, were incubated with a single concentration of nasal spray. Toxicity was observed in the top dilution (1/10). Virus was seen below that dilution so it did not affect calculations of virus titer or LRV. After a 25-minute contact time, the nasal spray (11% Pure Xylitol, 0.85%NaCL (Saline), and 0.20% grapefruit seed extract) reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reductio...
Pharmaceutics
In this time of COVID-19 pandemic, the strategies for prevention of the infection are a primary concern. Looking more globally on the subject and acknowledging the high degree of misuse of protective face masks from the population, we focused this review on alternative pharmaceutical developments eligible for self-defense against respiratory infections. In particular, the attention herein is directed to the nasal and oromucosal formulations intended to boost the local immunity, neutralize or mechanically “trap” the pathogens at the site of entry (nose or mouth). The current work presents a critical review of the contemporary methods of immune- and chemoprophylaxis and their suitability and applicability in topical mucosal dosage forms for SARS-CoV-2 prophylaxis.
Nasal vaccine as a booster shot: a viable solution to restrict pandemic?
Clinical and Experimental Vaccine Research
The coronavirus disease 2019 (COVID-19) pandemic revolutionized the vaccine market and initiated the momentum for alternative routes of administration for vaccines. The intranasal route of immunization is one such possibility that appears to be the most promising since it has some significant advantages, particularly in the prevention of respiratory infection. To analyze and summarize the role of nasal vaccines over conventional vaccines during COVID-19 and the need for the nasal vaccine as a booster shot. In this narrative review, the required data was retrieved using keywords "COVID-19," "Intranasal," "Immunity," "Nasal spray," and "Mucosal" in databases including PubMed, Scopus, Embase, Science Direct, and Web of Sciences. The results of the study showed that the nasal vaccines were both effective and protective according to the current researches approaching during the COVID-19 period and the preclinical and clinical phase trials prove the intranasal vaccination elicits more robust and crossprotective immunity than conventional vaccines. In this narrative review article, mechanisms across the nasal mucosa will be briefly presented and the current status of nasal vaccines during the COVID-19 pandemic is summarized, and advantages over traditional vaccines are provided. Furthermore, after exploring the primary benefits and kinetics of nasal vaccine, the potential for consideration of nasal vaccine as a booster dose is also discussed.
Nasal Irrigation in the COVID-19 Era
2021
DOI: 10.46998/IJCMCR.2021.13.000314 Abstract Rapid spread of SARS-CoV-2 to the community leading to the COVID-19 disease has undoubtedly changed individuals’ lives and attitudes and has threatened healthcare systems globally. SARS-CoV-2 attaches and initiates its lifecycle in the nasopharyngeal mucosa via infected droplet inhalation which leads to high viral loads and increased disease transmission and severity. Other than preventive vaccination, additional measures to mitigate both the transmission and progression of SARS-CoV-2 are currently sought. Nasal irrigation can prevent early transmission, minimize viral shedding and disease severity, and limit complications by mechanical washing-out of infectious particles present in the nasal cavities. Several publications have now proposed that both isotonic (0.9% NaCl) and hypertonic (>0.9% NaCl) solutions can be utilized for nasal lavage in COVID-19 patients. Considering that nasal irrigations are safe and easy to use, this nonpharm...