Spread of coronavirus suggested to stop nasal spray

Left: The usual process of fusion of the virus and the cell membrane using the S-protein of the coronavirus. Right: a lipopeptide (marked in red and blue) blocks a change in the S-protein structure and prevents the virus from entering the cell

Rory D. de Vries et al. / Science, 2021

Biologists from the United States and the Netherlands have proposed preventing the spread of covid by using a nasal spray with lipopeptides that block the fusion of the virus with the cell membrane. After applying the spray, the molecules must remain on the cells of the respiratory tract for 24 hours, preventing viruses from entering, and, thus, preventing infection in case of contact with the distributor of the virus. Authors of the work, published in Science, have successfully tested the effect of the substance in experiments on ferrets.

To enter a cell, the SARS-CoV-2 virus must approach its surface so that the viral envelope and cell membrane merged into one whole, letting in genetic information (“the insides of the virus”) into the cell. This process starts up using the spike protein (S-protein) of the coronavirus. When the S-protein collides with its target on the cell surface, it undergoes structural changes that bring the viral particle closer to the membrane, forcing them to join. Probably, if you block one of the key regions of the viral protein, you will get interrupt this process, preventing the virus from getting close to the membrane.

Scientists from Erasmus University of Rotterdam (Netherlands) and Columbia University (USA) under the leadership of Matteo Porotto, building on their previous research proteins with antiviral activity, proposed an original design. The researchers combined one or two copies of the viral S-protein inhibitor protein with cholesterol (a fatty molecule) and tested whether the resulting substances could protect animals from coronavirus infection.

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First, the authors of the work checked the distribution of the two variants of the construct in the body of mice one, eight hours or a day after intranasal or subcutaneous administration of the agent. Analyzes have shown that the molecule with two inhibitor proteins is better retained in the lungs than the monomeric molecule and is less efficiently absorbed into the blood. Scientists used it in further experiments.

Studies on airway epithelial cells showed low toxicity of the compound after six days of exposure to high concentrations (<20 percent at 100 micromolar), and did not show toxicity at a concentration sufficient to block 90 percent of viral particles (35 nanomoles).

Next, scientists tested the effect of the protective agent on ferrets, since these animals are ideal model to study aerosol transmission of the virus. Six ferrets were prophylactically injected with buffered lipopeptide with a nasal spray. The dose was 2.7 milligrams per kilogram of animal weight, which is enough to block 50 percent of viral particles. Twenty-four hours later, the animals were housed in cages containing covid-diseased ferrets, which exuded viral particles. Animals were also planted in the cages, which were injected with a placebo instead of a lipopeptide. Under these conditions, the virus could be transmitted through aerosols, animal feces, or through bites. A day later, the ferrets were resettled again, and the experimental individuals were injected with additional doses of lipopeptide.

On the 21st day of the experiment, ferrets that received a protective lipopeptide did not find antibodies to coronavirus, unlike animals from the control group. Thus, the tool has successfully shown a preventive effect by blocking the transmission of the virus.

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The authors of the work also note that the developed lipopeptides have a long shelf life, and they do not need to be stored at low temperatures. Such properties can help stop the spread of the coronavirus, even among populations that do not have access to medical care.

At the moment, the main hopes in containing the pandemic are pinned on the vaccination of the population. Recently in the magazine The Lancet were published results of the third phase of clinical trials of the Russian vaccine “Sputnik-V”. About the possible side effects of this and other coronavirus vaccines editors N + 1 told in the material “Suffering is inevitable?”.

Vera Sysoeva

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