Abstract: www.nature.com/scientificreports
OPEN
Astodrimer sodium nasal spray
forms a barrier to SARS‑CoV‑2
in vitro and preserves normal
mucociliary function in human
nasal epithelium
Jeremy R. A. Paull 1*, Carolyn A. Luscombe 1, Aynaz Seta 1, Graham P. Heery 1,
Michael D. Bobardt 2, Philippe A. Gallay 2, Samuel Constant 3 & Alex Castellarnau 1
COVID-19 remains a severe condition for many including immunocompromised individuals. There
remains a need for effective measures against this and other respiratory infections, which transmit
via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection
against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral
barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were
evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose
(HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays
simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell
monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized
to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS
reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human
nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary
clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while
HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates
an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral
infection in the nasal cavity.
Since the height of the COVID-19 pandemic, the severity of the condition has lessened, indicated by a decline
in mortality rates as well as a reduction in the proportion of patients hospitalized due to COVID-19 and that
require intensive medical intervention. This shift in COVID-19 morbidity and mortality patterns can be attributed to the widespread access to highly effective COVID-19 vaccines, a high level of immunity induced by prior
infection within the population, availability of outpatient treatment options and changes in the SARS-CoV-2
virus itself1. Despite these improvements in managing the spread and impact of COVID-19, it remains a severe
condition for many, particularly the elderly, unvaccinated or immunocompromised individuals, and those with
respiratory comorbidities. Therefore, the search for effective strategies to complement other preventive and therapeutic options and lessen the incidence and clinical severity of the disease as well as other respiratory infections,
including those that may emerge as potential pandemic viruses in future, is ongoing.
Respiratory viruses primarily transmit when an infected individual expels droplets laden with the virus a
short distance through the air. These droplets can either directly contact the nasal or oral mucous membranes
of a susceptible individual or be indirectly transferred through contact with contaminated s urfaces2–4. The first
line of defence against respiratory viral infections includes intrinsic mechanisms such as mucus production and
the innate immune system’s detection and response capabilities. The application of a nasal spray, designed to
provide..
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'abstract': '<jats:title>Abstract</jats:title><jats:p>COVID-19 remains a severe condition for many '
'including immunocompromised individuals. There remains a need for effective measures against '
'this and other respiratory infections, which transmit via virus-laden droplets that reach the '
'nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such '
'formulations should preserve normal nasal mucociliary function. The antiviral barrier '
'efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were '
'evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose '
'(HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). '
'Assays simulated clinical conditions. Antiviral barrier function and cell viability were '
'assessed in airway cell monolayers, while a model of fully differentiated human nasal '
'epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating '
'frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and '
'demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no '
'impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, '
'NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of '
'mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical '
'efficacy and safety profile as a barrier nasal spray against respiratory viral infection in '
'the nasal cavity.</jats:p>',
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