March 31, 2023 – An antiviral therapy in early development has the potential to stop COVID-19 infections when given as a nasal spray just 4 hours before exposure. New research shows it also works as a treatment when applied within the nose inside 4 hours of infection.
The antiviral drug often called TriSb92 (brand name Covidin, from the drug manufacturer Pandemblock Oy in Finland) also appears to be effective against all variants of coronavirus of concern and even neutralized the omicron variants BA.5, XBB and BQ.1.1 in laboratory and mouse studies.
Unlike a COVID vaccine, which boosts an individual's immune system for defense, the antiviral nasal spray works more directly by blocking the virus and acting as a “biological mask in the nasal cavity.” the biotechnology company set as much as develop the treatment.
The product targets a stable site on the virus's spike protein that shouldn’t be known to mutate. This site is present in lots of variants of the COVID virus, so it might be effective against future variants as well, researchers indicate.
“In animal models, TriSb92 provides immediate and robust protection” against coronavirus infection and severe COVID disease by directly inactivating the virus, said Anna R. Mäkelä, PhD, lead writer of the study and senior scientist within the Department of Virology on the University of Helsinki in Finland.
The study was published online on March 24 in Nature communication.
A possible first line of defense
Even in cases where the antiviral doesn’t prevent coronavirus infection, the treatment could decelerate the infection. It could achieve this by limiting the quantity of virus that may reproduce early within the skin within the nose and nasopharynx (the upper a part of the throat), said Mäkelä, who can be CEO of Pandemblock Oy, the corporate that developed the product.
“TriSb92 could tip the balance in favour of [the person] and thus help reduce the risk of severe COVID-19 disease,” she said.
The antiviral agent could also provide an alternative for people who do not respond or do not respond to vaccination.
“Many older people, as well as people who are immunocompromised for various reasons, do not respond to vaccines and require other protective measures,” said Kalle Saksela, MD, PhD, lead writer of the study and a virologist on the University of Helsinki.
Multiple doses required?
TriSb92 is “considered one of several approaches in the shape of nasal sprays, but probably not as long-lasting as effective nasal vaccines,” said Dr. Eric Topol, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Topol is also editor in chief of Medscape, WebMD's sister site for healthcare professionals.
“The sprays generally require multiple doses per day, while a single dose of a nasal vaccine can provide protection for months,” he said.
“Both have the appeal of being variant-safe,” added Topol.
Think small
Many laboratories are moving from treatments with monoclonal antibodies to treatments with smaller antibody fragments, so-called “nanobodies,” because they are less expensive and have a longer shelf life, Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell cultures or animal models, including as an intranasal preventive treatment against SARS-CoV-2.
One of these smaller antibodies is being developed by Lamas for example; another comes from Experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies of llamas and mice and showed that 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 the cells so that it looks like a virus has already attached itself to them. This is how the virus moves along.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. At the pre-administered dose, none of the treated mice had SARS-CoV-2 RNA in their lungs, while the untreated mice in the comparison group had “abundant” high levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective cell layer known as epithelium in the nose, nasal mucosa and respiratory tract.
A similar result was observed when TriSb92 was administered two to four hours after SARS-CoV-2 had already infected the epithelium, resulting in a complete lack of viral RNA in the lungs.
However, it was more effective against the virus when administered before infection rather than after, “perhaps as a result of the initial establishment of infection,” the researchers note.
The company, led by Mäkelä, is currently working to secure funding for human clinical trials of TriSb92.