Compounds that obstruct the “landing gear” of a range of harmful viruses can successfully protect against infection by the virus that causes COVID-19, new research has revealed.
Based on the findings, researchers have launched a human clinical trial of one such compound made by chemically stabilising a key coronavirus peptide.
If the stapled lipopeptide proves effective as a nasal spray in the trial, it could be the basis for a new drug modality to prevent or treat COVID-19, the authours said.
Stapled lipopeptides may also be effective against dangerous and potentially deadly viruses such as RSV, Ebola, and Nipah, the authors demonstrated in the study.
Loren Walensky, MD, PhD is Physician and Principal Investigator, Linde Program in Cancer Chemical Biology at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.
He said: “Although vaccines, monoclonal antibodies, and small molecule drugs have played a crucial role in protecting people from life-threatening COVID-19 infection, there remains a critical gap in the treatment arsenal.
“The constant evolution of the virus and the emergence of new variants has markedly decreased the effectiveness of immune-based approaches, requiring periodic reformulation of vaccines.
“What has been missing are fast-acting, easy-to-administer, and resistance-proof agents that can be used before or after exposure to the virus to directly prevent infection or reduce symptoms.
Unlike mRNA vaccines, which are a form of immune-based therapy that provides delayed protection and also requires periodic administration due to viral mutation and/or waning immunity, the stapled lipopeptides developed by the researchers act directly on SARS-CoV-2, the coronavirus responsible for COVID-19, interfering with its ability to infect healthy cells.
Because the approach does not use the immune system as an intermediary, it is particulatly promising for people with weakened immune systems, either due to their disease or treatment with immunosuppressive agents, such as chemotherapy.
Walensky’s lab has pioneered the development and application of stapled peptides for nearly 20 years.
These unique agents consist of natural peptides – a stretch of amino acids in a defined sequence – whose bioactive structure is chemically stabilised by an installed “staple” and, in this case, further linked to a lipid, which is believed to help concentrate the stapled peptide at the site of viral infection – the membrane surface of the otherwise healthy cell.
The new study shows that stapled lipopeptides are exceptionally stable, resisting extremes of temperature and chemical conditions – an important feature for persistence both inside and outside the body.
This design strategy not only prevents peptide degradation in the body upon administration, but also remedies prior challenges with shipment and storage, such as the required cold chain for COVID-19 vaccines.
Walensky said: “This approach has the potential to fill an important gap in our arsenal against COVID-19 and other viruses that cause severe respiratory and hemorrhagic diseases.
“Imagine being able to protect yourself from COVID-19 or other disruptive respiratory viruses with a simple nasal spray that you could use to avoid infection at a large gathering or after exposure to a close contact who turns out to test positive for SARS-CoV-2.
“That is the promise this work holds, not only for otherwise healthy individuals, but especially for immunocompromised patients who remain most at risk of severe infection.”
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