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  • Eszter Nagy, MD, PhD

Nasal sprays – an alternative approach to protect against COVID-19

Updated: Oct 13, 2021

Although vaccination is the most practical approach for infectious disease control, there are challenges to achieve herd immunity with anti-COVID vaccines currently in development. An alternative approach is the prevention or removal of nasal colonisation via application of an antiviral on the nasal mucosa.

COVID-19 is caused by SARS-CoV-2, a respiratory virus that targets the nasal mucosa as the primary infection site in the human body. SARS-CoV-2 spreads mainly through droplets of saliva or discharge from the nose when an infected person coughs or sneezes. The coronavirus infection begins with the attachment of the viral particles to the host cell via the viral Spike glycoprotein. SARS-CoV-2 utilizes the human Angiotension-Converting Enzyme 2 (ACE2) protein as its primary receptor for viral entry. As recently reported (, the highest ACE2 expression is found in the nose, while progressively reduced amounts of ACE2 expression are observed in the lower airway regions. Clinical data from COVID-19-positive subjects support the concept of early infection in the upper respiratory tract, followed by subsequent aspiration and infection of the lower respiratory tract and finally the lung. It has been shown that the nasal cavities and nasopharynx harbour a significant amount of SARS-CoV-2, even in asymptomatic or presymptomatic carriers of the virus. Therefore, inhibiting the colonization and infection of the nasal mucosa, or removal of the virus from there, represents an attractive approach to prevent SARS-CoV-2 infection in lower respiratory system and development of disease, which can induce massive inflammation in the lungs leading to life threatening conditions.

Drug repurposing is an important strategy for immediate response to the COVID-19 pandemic. In this approach, the main goal of computational and experimental studies has been to find existing drugs that might be effective against SARS-CoV-2. CEBINA’s drug repurposing approach has led to the identification of azelastine, an anti-histamine, with potent anti-SARS-CoV-2 activity in human nasal tissue model. Azelastine-HCl is a second generation anti-histamine drug for the alleviation of allergy; it is a fast-acting and well-tolerated selective antagonist of the histamine H1-receptor, widely available as nasal spray. Azelastine has shown potent anti-SARS-CoV-2 activity also at concentrations lower than the commercially available ones ( and has recently been identified in a preprint manuscript as an inhibitor the protease of SARS-CoV-2 (, responsible for proteolysis of polyproteins translated from the viral genome into non-structural proteins essential for packaging the nascent virion and therefore viral replication.

Notably, azelastine also has general anti-inflammatory effects, mainly exerted via mast cell stabilization and inhibition of leukotriene and pro-inflammatory cytokine production. Mast cells are the main sources of cytokine release that leads to lung damage in SARS-CoV-2 and it has been speculated that mast cell stabilisers may also attenuate pulmonary complications, fatal inflammation and death in COVID-19. Therefore, azelastine’s potential beneficial effects in COVID-19 are expected to be the combination of antiviral and host-mediated actions.

Update 17th August 2021: CEBINA has jointly sponsored a Phase 2 efficacy study, demonstrating that a nasal spray containing the active ingredient azelastine was effective in accelerating the reduction of the viral load in SARS-CoV-2 positive patients.

Read more about the Azelastine clinical trial here.

As we witness the beginning of a second wave of coronavirus infections, with record rises in the number of new cases registered daily, the confirmation of the anti-SARS-CoV-2 activity of azelastine in COVID-19 patients, azelastine could be of immediate impact in the global fight against the coronavirus pandemic. Widespread application of azelastine nasal formulations could prevent and treat nasal colonization with SARS-CoV-2, therefore controlling the viral spread within the population and preventing the nasal infection from developing into symptomatic and severe form of COVID-19.

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