Researchers at the Gladstone Institutes have in the past developed a new technique for the treatment of infectious diseases: a single-dose intranasal remedy that protects against severe SARS-CoV-2 infection.
In a new paper published in the Proceedings of the National Academy of Sciences, they show that this new treatment, called a curative interference particle (TIP), also reduces the amount of virus excreted by inflamed animals and limits transmission of the virus.
“Historically, it has been exceptionally complicated for antivirals and vaccines to restrict respiratory virus transmission, adding SARS-CoV-2,” says Gladstone principal investigator Leor Weinberger, Ph. D. , leader of the new paper. “This study shows that a single intranasal dose of TIP reduces the amount of virus transmitted and protects animals that have been in contact with this treated animal. “
“To our knowledge, this is the only single-dose antiviral that reduces only the symptoms and severity of COVID-19, but also the loss of the virus,” says Sonali Chaturvedi, Ph. D. , a Gladstone researcher and first author. paper.
A drug that evolves
Viruses such as SARS-CoV-2, as well as influenza and HIV, evolve over time, are resistant to drugs, and hinder the expansion of sustainable treatments. More than two decades ago, Weinberger first proposed the concept of interfering component cure (TIP) to treat viruses; Instead of directly targeting the component of a virus, TEPs compete for resources in an inflamed cell. By monopolizing a cell’s internal replication machinery, they can prevent the virus from generating more copies of itself.
However, the advantages of obtaining TIP go beyond its ability to suffocate the inflamed cells inside a virus. Because TIP lives within the same cells as the virus they target, it evolves at the same time, remaining active even when new viral strains emerge. .
“In recent years, many of the demanding situations of the pandemic have been similar to the emergence of new variants,” says Chaturvedi. the challenge of drug resistance. “
Before the COVID-19 pandemic, Weinberger’s organization already introduced TIP to treat HIV. In 2020, they temporarily turned to SARS-CoV-2, presenting a single-dose TIP opposite to the virus that can be administered intranasally.
Last year, they reported that, in rodents, TIP can effectively block several other variants of SARS-CoV-2, reducing the viral load in the lungs a hundred times and reducing many COVID-19 symptoms.
Stop the spread
In the new paper, Weinberger and Chaturvedi investigated whether TIP may also be a viral loss, a separate factor from reduced symptoms and viral load.
The researchers treated the hamsters inflamed by SARS-CoV-2 with antiviral TIP and then measured, daily, the amount of virus in the animals’ noses. Compared to hamsters who had not won TIP (called animals), the treated animals had fewer viruses in their nostrils at any given time. On day 5, all animals were still excreting high levels of the virus, while the virus was undetectable in 4 of the five animals treated with TIP.
“We know that the amount of virus excreted is proportional to a person’s degree of infection,” says Weinberger, who is also William and Ute Bowes Professor Emeritus and director of the Center for Cellular Circuits at Gladstone. “If viral loss can be reduced, the number of secondary contacts vulnerable to infection will also be reduced to the maximum, which in turn will minimize the overall spread of the virus and ensure the protection of vulnerable people. “
When animals inflamed with SARS-CoV-2 were housed in cages with non-inflamed animals, treating inflamed animals with TIP absolutely did not save COVID-19 transmission. However, this resulted in a significant reduction in viral amount and milder infection symptoms. in newly exposed animals.
“This specific laboratory environment is known to generate much more effective transmission than is observed in humans, even in homes, as hamsters transmit not only through aerosols, but also through physical fluids and climbing on them and grooming for many hours. “says Weinberger, who is named Professor of Biochemistry and Biophysics and Pharmaceutical Chemistry at UC San Francisco. “Therefore, being able to decrease the transmission of SARS-CoV-2 in this animal environment is promising enough to be able to decrease human transmission. transmission to humans. “
While initial experiments were conducted with the Delta strain of SARS-CoV-2, the researchers repeated tests with the ancestral WA-1 strain of the virus and showed that the same TIP was effective in all variants.
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