Recently, researchers have been studying how to prevent the new coronavirus from entering host cells. The antiviral lipopeptide is cheap to produce, has a long shelf life, and does not require refrigeration. These features make it stand out from other antiviral methods under development, including many monoclonal antibodies. The new nasal lipopeptide may be an ideal choice to prevent the global spread of the new coronavirus, and this transportable and stable compound is especially critical for low-income people in remote areas that are difficult to reach. This study was recently published in the journal Science.
Ferrets are often used to study respiratory diseases because the lungs of this animal are similar to humans. Ferrets are highly susceptible to SARS-CoV-2, and the virus can easily spread between ferrets.
In this research conducted in collaboration with Dr. Rory de Vries and Dr. Rik de Swart of Erasmus University in the Netherlands, 100% of untreated ferrets were infected with the virus released, similar to the close contact in our human world Living environment.
Researchers have previously created similar lipopeptides-a small protein linked to cholesterol or tocopherol molecules to prevent other viruses from infecting cells, including measles, parainfluenza, and Nipah virus. These antiviral compounds are used in Human trials have been quite challenging.
A paper previously published in the journal mBio described the first-generation compound and its role in a 3d human lung model for the first time. In this human lung model, the compound can eliminate the initial infection, prevent the virus from spreading in the lung, and is completely non-toxic to airway cells.
The working principle of lipopeptides is to prevent the virus from fusing with the host cell membrane, which is a necessary step for enveloped viruses including SARS-CoV-2 to infect cells. In order to fuse, the new coronavirus first unfolds its spike protein and then shrinks into a bunch to drive the fusion.
The compound designed by Porotto and Moscona can recognize the spikes of SARS-CoV-2, wedges itself into the unfolding area, and prevents the formation of the compact shape necessary for spike protein fusion.
In the ferret experiment, lipopeptides were sent into the noses of six ferrets. Then, the treated ferrets were bred together with two control ferrets. The control ferret received normal saline nasal spray, and the other ferret was infected with SARS-CoV-2.
After 24 hours of intense direct contact between ferrets, tests showed that none of the ferrets under treatment had contracted the virus from the infected partner, their viral load was zero, and all control animals were highly virus infection.
Public health organizations are concerned about the emergence of several SARS-CoV-2 variants, which seem to be more contagious and lethal, and may be better at avoiding antibodies produced by existing therapies and vaccines.
Porotto and Moscona tested lipopeptides on cells infected with a series of SARS-CoV-2 variants (including B.1.1.7 and B.1.351) and found that the compound was as effective as the dominant strain in preventing spikes in all variants The protein fuses with the cell membrane.
Porotto and Moscona proposed that these peptides can be used in any situation that uninfected people may come into contact with, whether in the home, school, hospital, or community.
The researchers said that even under ideal circumstances, most of the population is vaccinated and fully comply with the vaccination procedures, these antiviral drugs will also become an important supplement to protect individuals and control transmission. People who cannot be vaccinated or who have not developed immunity especially benefit from this spray.
This antiviral drug is easy to use, and according to scientists’ experience with other respiratory viruses, its protective effect will take effect immediately and last for at least 24 hours.
Scientists are currently conducting detailed studies on the dissemination of animal models and the production and formulation of peptides. They hope that this preventive method can be used in human clinical trials as soon as possible. The ultimate goal is to fully deploy this therapy to help control the pandemic. During the period of spread, and can prepare and support for new emerging strains and pandemics in the future.
Inhalation preparations are unique in terms of technology development and review and approval. It is necessary to comprehensively consider the product’s prescription technology, quality control, drug delivery device, industrial production, and clinical application. Medicilon is familiar with the development process of various inhalation preparations, especially in the field of inhalation powder inhalation (DPI), nebulized inhalation and nasal spray (Nasal Spray) preparations. COPLEY’s new generation of medicinal impactor (NGI), COPLEY’s BRS2100 breathing simulator, Germany’s Sinpatec laser particle size analyzer, etc., can meet the quality research and in vitro evaluation of various inhalation preparations. Medicilon has a complete preclinical research platform for inhaled drug delivery, including pharmacokinetic tests and efficacy tests of inhaled drugs; at the same time, it can complete the safety evaluation of a complete set of drugs, such as tissue distribution test, acute toxicity test, repeated administration toxicity test , Irritation test, allergy test and safety pharmacological test, etc. Medicilon will continue to pay attention to the progress of this research, hoping to help the research and development of inhaled drugs.
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