Small study develops non-toxic nasal spray prevents COVID-19 infection in ferrets

A nasal spray that blocks the absorption of the SARS-CoV-2 virus has completely protected ferrets it was tested on, according to a small study released Thursday by an international team of scientists. The study, which was limited to animals and has not yet been peer-reviewed, was assessed by several health experts at the request of The New York Times.

If the spray, which the scientists described as nontoxic and stable, is proved to work in humans, it could provide a new way of fighting the pandemic. A daily spritz up the nose would act like a vaccine.

“Having something new that works against the coronavirus is exciting,” said Dr Arturo Casadevall, the chairman of immunology at the Johns Hopkins Bloomberg School of Public Health, who was not involved in the study. “I could imagine this being part of the arsenal.”

The work has been underway for months by scientists from Columbia University Medical Center in New York, Erasmus Medical Center in the Netherlands and Cornell University in Ithaca, New York. The study was funded by the National Institutes of Health and the Columbia University Medical Center.

The team would require additional funding to pursue clinical trials in humans. Dr Anne Moscona, a paediatrician and microbiologist at Columbia and co-author of the study, said they had applied for a patent on the product, and she hoped Columbia University would approach the federal government’s Operation Warp Speed or large pharmaceutical companies that are seeking new ways to combat the coronavirus.

The spray attacks the virus directly. It contains a lipopeptide, a cholesterol particle linked to a chain of amino acids, the building blocks of proteins. This particular lipopeptide exactly matches a stretch of amino acids in the spike protein of the virus, which the pathogen uses to attach to a human airway or lung cell.

Before a virus can inject its RNA into a cell, the spike must effectively unzip, exposing two chains of amino acids, in order to fuse to the cell wall. As the spike zips back up to complete the process, the lipopeptide in the spray inserts itself, latching on to one of the spike’s amino acid chains and preventing the virus from attaching.

“It is like you are zipping a zipper but you put another zipper inside, so the two sides cannot meet,” said Matteo Porotto, a microbiologist at Columbia University and one of the paper’s authors.

The work was described in a paper posted to the preprint server bioRxiv Thursday morning and has been submitted to the journal Science for peer review.

Dr Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, said the therapy looked “really promising.”

“What I’d like to know now is how easy it is to scale production,” he said.

In the study, the spray was given to six ferrets, which were then divided into pairs and placed in three cages. Into each cage also went two ferrets that had been given a placebo spray and one ferret that had been deliberately infected with SARS-CoV-2 a day or two earlier.

Ferrets are used by scientists studying flu, severe acute respiratory syndrome and other respiratory diseases because they can catch viruses through the nose much as humans do, although they also infect each other by contact with faeces or by scratching and biting.

After 24 hours together, none of the sprayed ferrets caught the disease; all the placebo-group ferrets did.

“Virus replication was completely blocked,” the authors wrote.

The protective spray attaches to cells in the nose and lungs and lasts about 24 hours, Moscona said. “If it works this well in humans, you could sleep in a bed with someone infected or be with your infected kids and still be safe,” she said.

The amino acids come from a stretch of the spike protein in coronaviruses that rarely mutates. The scientists tested it against four different variants of the virus, including both the well-known “Wuhan” and “Italian” strains, and also against the coronaviruses that cause SARS and the Middle East respiratory syndrome.

In cell cultures, it protected completely against all strains of the pandemic virus, fairly well against SARS and partially against MERS.

The lipoprotein can be inexpensively produced as a freeze-dried white powder that does not need refrigeration, Moscona said. A doctor or pharmacist could mix the powder with sugar and water to produce a nasal spray.

Other labs have designed antibodies and “mini-proteins” that also block the SARS-CoV-2 virus from entering cells, but these are chemically more complex and may need to be stored in cold temperatures.

Moscona and Porotto have been collaborating on similar “fusion inhibitor” peptides for 15 years, they said in a conference call. They have developed some against measles, Nipah, parainfluenza and other viruses.

But those products aroused little commercial interest, Porotto said, because an effective measles vaccine already exists and because the deadly Nipah virus only turns up occasionally in faraway places like Bangladesh and Malaysia.

Monoclonal antibodies to the new coronavirus have been shown to prevent infection as well as treat it, but they are expensive to make, require refrigeration and must be injected. Australian scientists have tested a nasal spray against COVID-19 in ferrets, but it works by enhancing the immune system, not by targeting the virus directly.

Because lipopeptides can be shipped as a dry powder, they could be used even in rural areas in poor countries that lack refrigeration, Moscona said.

Moscona, a paediatrician who usually works on parainfluenza and other viruses that infect children, said she was most interested in getting the product to poor countries that may never have access to the monoclonal antibodies and mRNA vaccines that Americans may soon have. But she has little experience in that arena, she said.

“I’ve always been a basic scientist,” she said. “I’ve never done drug development or taken anything to the FDA or anything like that.”

Donald G. McNeil Jr. c.2020 The New York Times Company

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