US Pharm. 2022;47(10):1.

Scientists from Cleveland Clinic’s Florida Research and Innovation Center (FRIC) found that disrupting a cellular structure called the actin cytoskeleton is a “priming signal” for the body to respond to a virus. These findings, published in Cell in September, potentially lay the groundwork for developing new antiviral vaccines and treatments.

Previously, viral genetic material such as RNA was considered the sole requirement for certain sensor molecules that live in cells to trigger an immune response—an “alarm system” for many types of cells. RNA also serves as a basis for vaccines through training a patient’s immune system to recognize a virus. This new study evidences that the signaling process also requires disrupting the actin cytoskeleton inside cells, which happens when a virus infects cells.

“It’s a fundamental new way of considering how the immune system can be activated, and the implications are that this could lead to broad antiviral therapeutics,” said Michaela Gack, PhD, the Arthur and Marylin Levitt endowed chair and scientific director of the FRIC. “Our data show this process is common across different types of RNA viruses.”

Composed of the protein actin, cytoskeletons serve as structural support for cells but are also key in cells’ ability to grow, divide, and internalize key substances. A virus disturbs the cytoskeleton, but so can vaccine components and certain therapeutics, Dr. Gack noted.

“Whether this process is sensed by our cellular immune surveillance system and can trigger an antiviral response has been unknown,” said Dr. Gack. “Our work showed that specific immune receptors sense actin cytoskeleton rearrangements induced by viruses and then trigger alarm.”

Despite being around for decades, interest in using RNA as the basis for vaccines and therapeutics grew exponentially during the COVID-19 pandemic. The research revealed that the triggering system is similar across multiple viruses, including Zika, influenza, or SARS-CoV-2.

Dr. Gack’s team, including lead author Dhiraj Acharya, PhD, research associate at FRIC, also discovered that lipid components or virus-like particles such as those used in vaccines or RNA-based therapeutics can cause the cytoskeletal disturbance necessary for prompting an immune response. These results could help developers fine-tune the immunostimulatory potencies of therapeutics or vaccines.

Dr. Gack’s laboratory, operating under Cleveland Clinic’s multisite Global Center for Pathogen Research and Human Health, a cornerstone of the Cleveland Innovation District, investigates virus-host interactions on a molecular level, identifying host responses that can play a key role in developing new treatments and vaccines.

This comprehensive issue of U.S. Pharmacist, which focuses on new drugs, reports on several recently approved antivirals and other pharmaceuticals with applications in outpatient and inpatient settings.

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