March 31, 2023 – An antiviral therapy in early development has the potential to prevent COVID-19 infections when given as a nasal spray as little as 4 hours before exposure. It also appears to work as a treatment if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a "biological mask in the nasal cavity," according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the Department of Virology at the University of Helsinki in Finland.
The study was published online March 24 in Nature Communications.
A Potential First Line of Defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines, and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple Doses Needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, CA. Topol is also editor-in-chief of Medscape, WebMD's sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Topol added.
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called "nanobodies" because they are more cost-effective and are able to last longer in storage, Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus's RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection," the researchers note.
The company led by Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.