Like savvy international travelers, viruses know exactly how to pack. With the genetic instructions for the next generation folded up like that, stuck in an outer covering made with cell-capturing proteins, these little invaders look for new digs in the region. When they find them, they get to work. Each newly infected cell soon releases thousands of perfectly packaged fresh-faced viral particles, fueling the exponential growth of an infection.
Now, a Stanford Medicine study of influenza and SARS-CoV-2, the virus that causes COVID-19, shows that antiviral drugs that disrupt this game of genomic Tetris can slow infections. At the same time, these drugs allow sufficient exposure to the virus to trigger a natural immune response that confers lasting protection.
Because tried-and-true packaging strategies are shared among viral family members, an antiviral drug can be effective against several closely related viruses, such as seasonal influenza A, swine flu, and bird flu. And because it’s difficult to reformulate a three-dimensional puzzle, viruses are unlikely to become resistant to a treatment that takes advantage of this tactic.
These antivirals can be adapted to almost any virus. They provide immediate protection when administered before or after exposure, and stimulate a long-lasting immune response that neutralizes a subsequent challenge of even a ten-fold lethal dose of influenza. This is really exciting.”
Jeffrey Glenn, MD, PhD, Professor of Microbiology and Immunology
The study, which was carried out in mice, hamsters and human cells grown in the laboratory, was published online in Natural Medicine August 18 Glenn, the Joseph D. Grant Professor II, is the lead author of the study. Research scientist Rachel Hagey, PhD, is the paper’s lead author.
A tool for the next pandemic
The discovery suggests the possibility of quickly halting the spread of some of humanity’s deadliest viruses with custom antivirals designed, manufactured and stockpiled before the next outbreak occurs.
The findings are the first to come out of Stanford’s newly formed SyneRx, which is one of nine antiviral drug discovery centers for pathogens of pandemic concern funded by the National Institute of Allergy and Infectious Diseases, and [email protected], which is Stanford Medicine’s Biosecurity and Pandemic Preparedness Initiative. Glenn leads the center, which received $69 million in May to help design antivirals to fight COVID-19 and other diseases with the potential to cause future pandemics.
Vaccines that fight viruses tend to encourage the body’s immune system to recognize and react to critical viral proteins, such as the SARS-CoV-2 spike protein. But as has become apparent during the ongoing pandemic, proteins can mutate in subtle ways to evade the immune system, leading to breakthrough infections in vaccinated people.
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Journal reference:
Hagey, RJ, et al. (2022) Programmable antivirals targeting critical conserved viral RNA secondary structures of influenza A virus and SARS-CoV-2. Natural Medicine. doi.org/10.1038/s41591-022-01908-x.