by Researchers from the Dana-Farber Cancer Institute have conducted a study showing that compounds capable of obstructing the entry of various harmful viruses can effectively protect against COVID-19 infection. These compounds, known as stapled lipopeptides, have been chemically stabilized, and one variant is currently undergoing a human clinical trial as a nasal spray. If proven effective in the trial, the compound could potentially serve as the basis for a new drug modality for preventing or treating COVID-19. The study, published in the journal Nature Communications, also suggests that stapled lipopeptides may be effective against other dangerous viruses, such as RSV, Ebola, and Nipah.
The researchers highlighted that while vaccines, monoclonal antibodies, and small molecule drugs have played a crucial role in protecting individuals 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 have significantly reduced the effectiveness of immune-based therapies, necessitating periodic reformulation of vaccines. Therefore, the development of fast-acting, easy-to-administer, and resistance-proof agents is crucial in preventing infection or reducing symptoms directly. The findings of this study suggest that stapled lipopeptides may offer potential in addressing this need.
Unlike mRNA vaccines, which provide delayed protection and require periodic administration due to viral mutation and waning immunity, stapled lipopeptides do not rely on the immune system for their mechanism of action. This makes them particularly promising for individuals with weakened immune systems, such as those undergoing immunosuppressive therapy.
The stability of stapled lipopeptides is also a significant advantage. They have demonstrated resistance to extremes of temperature and chemical conditions, making them suitable for use both inside and outside the body. Furthermore, their design allows for better peptide degradation prevention upon administration, as well as addressing challenges related to shipment and storage, such as the cold chain requirements of COVID-19 vaccines.
The development of stapled peptides for virus inhibition is not a new concept for the researchers. In 2010, they developed double-stapled peptides that targeted the human immunodeficiency virus (HIV) by disrupting the formation of the fusion apparatus that allows the virus to infect human cells. They later developed stapled peptides targeting the respiratory syncytial virus (RSV), demonstrating their effectiveness in preventing RSV infection in mice.
When the COVID-19 pandemic emerged, the researchers promptly adapted their approach to target the SARS-CoV-2 virus. They began developing numerous stapled peptide fusion inhibitors, altering the staple location and linker between the staple and the lipid to optimize effectiveness against a broad spectrum of SARS-CoV-2 variants. The results of animal studies using hamsters were encouraging, as nasal treatment with the stapled peptide fusion inhibitor prevented infection from adversely affecting the lungs and causing severe disease. In addition, the inhibitors showed promise in reducing transmission from one hamster to another.
Red Queen Therapeutics, a company that has licensed the technology from Dana-Farber, has initiated human trials on the stapled lipopeptides for SARS-CoV-2. The company expects to have data to share later in the quarter. The researchers believe that this approach has the potential to fill an important gap in the fight against COVID-19 and other respiratory and hemorrhagic viruses. The ability to prevent infection using a simple nasal spray could be transformative, particularly for immunocompromised patients who are at higher risk of severe infection.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
