New Delhi: An international team of researchers have developed a new protein-based antiviral nasal spray, which is being advanced toward Phase I human clinical trials to treat Covid-19.
The new protein therapies have been designed computationally and refined in the laboratory. They fight against Covid-19 infection by interfering with the ability of SARS-CoV-2 to enter host cells.
The study, led by researchers at Northwestern University, University of Washington, and Washington University in St Louis, was recently published in the journal Science Translational Medicine.
According to the study, the top protein neutralised the virus with similar or greater potency than antibody treatments with Emergency Use Authorisation (EUA) status from the US Food and Drug Administration (FDA).
The Protein Neutralises All Tested SARS-CoV-2 Variants
Another interesting finding was that the top protein neutralised all tested SARS-CoV-2 variants, which is something many clinical antibodies have failed to do.
The study authors administered the treatment to mice as a nasal spray, and observed that the best of these antiviral proteins reduced symptoms of infection. The antiviral proteins also prevented infection.
Researchers Designed Proteins That Could Attach To Vulnerable Sites On SARS-CoV-2
Initially, the scientists used supercomputers to design proteins that could attach to vulnerable sites on the surface of SARS-CoV-2, targeting the spike protein. The findings were originally reported in 2020 in the journal Science.
What Are Minibinders?
In the new study, the researchers reengineered the proteins, which are called minibinders, to make them more potent. The minibinders do not target just one site of the virus' host machinery, but simultaneously bind to three sites. This makes the drug less likely to detach, according to the study.
Current Antibody Treatments Block Just One Domain On SARS-CoV-2’s Spike Protein
In a statement issued by Northwestern University, Michael Jewett, one of the study authors, said SARS-CoV-2's spike protein has three binding domains, and common antibody therapies may block just one domain.
How Do Minibinders Work?
He explained that the minibinders sit on top of the spike protein like a tripod and block all three. The interaction between the spike protein and the antiviral developed by the researchers is among the tightest interactions known in biology.
Jewett said that when the team put the spike protein and the antiviral therapeutic in a test tube together for a week, they stayed connected and never fell apart.
Since SARS-CoV-2 has mutated into new variants, some treatments have become less effective in fighting the virus, which keeps evolving. The FDA halted several monoclonal antibody treatments last month, due to their failure against the BA.2 Omicron sub-variant, the statement said.
The antibody treatments failed to neutralise Omicron. Unlike them, the new minibinders maintained potency against the Omicron variant of concern.
The new antiviral blocks the virus' spike protein, and prevents it from binding to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is the entry point for SARS-CoV-2 to infect the body.
Since the novel coronavirus and its mutant variants cannot infect the body without binding to the ACE2 receptor, the antiviral also should work against future variants, the study said.
Jewett explained that to enter the body, the spike protein and ACE2 receptor engage in a handshake. The antiviral developed by the researchers blocks this handshake, and as a bonus, has resistance to viral escape.
Current antibody therapies come with several problems, including losing effectiveness. Moreover, they are difficult to develop, expensive, and require a healthcare professional to administer. Also, they require complicated supply chains and extreme refrigeration, which is often unavailable in low-resource settings, according to the study.
How Is The New Antiviral A Boon?
The new antiviral is a boon because it solves all these problems. Monoclonal antibodies are made by cloning and culturing living mammalian cells. Unlike them, the new antiviral treatment is produced large-scale in microorganisms like Escherichia coli.
This makes the new antiviral treatment cost-effective to manufacture. The new therapy is stable in heat, and this could further streamline manufacturing and decrease the cost of goods for clinical development. The therapy also holds promise for being self-administered as a one-time nasal spray, bypassing the requirements for medical professionals, the study said.
The researchers believe that the nasal spray could soon be available at the pharmacy and used as a preventive measure to treat Covid-19 infection.
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