Could a nasal spray prevent the transmission of the coronavirus?

A nasal antiviral created by researchers at Vagelos College of Physicians and Surgeons at Columbia University has blocked the transmission of SARS-CoV-2 in ferrets, suggesting that the nasal spray may also prevent infection in people exposed to the new virus. coronavirus.

The compound in the spray – a lipopeptide developed by Anne Moscona, MD, and Matteo Porotto, Ph.D., professors in the Department of Pediatrics and directors of the Center for Host-Pathogen Interaction – is designed to prevent the novel coronavirus from entering host cells.

The antiviral lipopeptide is inexpensive to produce, has a long shelf life and does not require refrigeration. These characteristics distinguish it from other antiviral approaches in development, notably monoclonal antibodies. New Nasal Lipopeptide Could Be Great For Stopping The Spread Of COVID In The United States And Around The World; the transportable and stable compound could be particularly important in rural, low-income and hard-to-reach populations.

A preprint of the study appeared in bioRxiv on November 5; an article describing a first generation of the compound and its effect in a 3-D model of the human lung first appeared in the journal mBio October 20. In this model of a human lung, the compound was able to quench an initial infection, prevent the virus from spreading in the lungs, and was not at all toxic to airway cells.

Ferrets a role model for respiratory disease

Ferrets are often used in studies of respiratory disease because the lungs of these animals and humans are similar. Ferrets are very susceptible to infection with SARS-CoV-2, and the virus is easily spread from ferret to ferret.

In this study, 100% of untreated ferrets were infected through their virus-shedding cagemates, approaching a setting like sharing a bed or close living conditions for people.

Moscona and Porotto have previously created similar lipopeptides – small proteins bound to a cholesterol or tocopherol molecule – to prevent infection of cells with other viruses, including the measles, parainfluenza, and Nipah viruses. These antiviral compounds have been difficult to bring to human trials, in large part because the infections they prevent are most prevalent or severe in low-income settings.

When SARS-CoV-2 emerged earlier this year, researchers adapted their designs to the new coronavirus. “One lesson we want to highlight is the importance of applying basic science to develop treatments for viruses that affect human populations around the world,” say Moscona and Porotto. “The fruits of our previous research have led to our rapid application of the methods to COVID-19.”

Lipopeptides prevent viruses from infecting cells

Lipopeptides work by preventing a virus from fusing with its host’s cell membrane, a necessary step that enveloped viruses, including SARS-CoV-2, use to infect cells. To fuse, the new coronavirus deploys its spike protein before contracting into a compact bundle that results in fusion.

The compound designed by Moscona and Porotto recognizes the SARS-CoV-2 spike, gets stuck in the unfolded region, and prevents the spike protein from assuming the compact shape needed for fusion.

In the ferret experiments, the lipopeptide was administered into the nose of six ferrets. Pairs of treated ferrets were then housed with two control ferrets who received a nasal saline spray and a ferret infected with SARS-CoV-2.

After 24 hours of intense direct contact between the ferrets, testing revealed that none of the treated ferrets caught the virus from their infected cagemate and their viral load was precisely zero, while all of the control animals were heavily infected.

Lipopeptides are easily administered

Moscona and Porotto propose that these peptides could be used in any situation where an uninfected person would be exposed, whether in a home, school, health care setting or community.

“Even in an ideal scenario with large segments of the population vaccinated – and with complete confidence and adherence to vaccination procedures – these antivirals will be an important addition to protect individuals and control transmission,” Moscona and Porotto say. People who cannot be vaccinated or who do not develop immunity will particularly benefit from the spray.

The antiviral is easy to administer, and scientists have shown experience with other respiratory viruses that protection is immediate and lasts for at least 24 hours.

Scientists hope to quickly advance the preventive approach of human trials to contain transmission during this pandemic.