New antiviral peptide targets achilles heel of SARS-CoV-2

Researchers at Emory Vaccine Center have uncovered a potential weakness in SARS-CoV-2, the virus responsible for COVID-19. They’ve pinpointed a component of the virus’s fusion machinery that remains consistent across various viral variants. This vulnerable machinery is the target of an antiviral peptide called Yongshi, derived from a natural peptide found in wild boars. Yongshi has shown promise in preventing SARS-CoV-2 from infecting host cells and is effective against multiple variants, including XBB.1.16, as well as related viruses like SARS-CoV-1 and MERS. Unlike monoclonal antibodies that lose efficacy with viral evolution, Yongshi could offer a more adaptable approach to antiviral treatment.

The origins of Yongshi can be traced to cathelicidin peptides found in various animals. Researchers, led by senior author Joshy Jacob, selected a peptide from wild boars due to its high activity and then modified it to reduce its toxicity to human cells. Computational simulations and lab experiments helped unveil how Yongshi interacts with the SARS-CoV-2 spike protein, specifically the “helical bundle.” This discovery is significant as it suggests that previously known helical bundle peptide inhibitors might not be effective in individuals who have been vaccinated or have recovered from COVID-19.

Jacob’s lab has a history of discovering antiviral peptides from nature, including one from frog skin secretions that combat flu, Zika, and dengue viruses. However, translating these peptides into effective drugs poses challenges due to enzymatic degradation in the body.

To make Yongshi a viable therapeutic option, further modifications may be necessary, such as chemical alterations to enhance stability and reduce required dosages. Jacob also suggests exploring mRNA technology, similar to that used in COVID-19 vaccines, for delivering Yongshi as a long-term treatment option, either post-infection or as a preventive measure.

Source: Emory University

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