Published on February 18, 2026, a major new study reveals an unexpected role for a key HIV protein that could open up new avenues for antiviral drug development. Researchers led by Professor Juan R. Perilla at the University of Delaware and collaborators in the United States and United Kingdom have discovered that the HIV protein integrase plays a previously unknown structural role early in the virus’s life cycle — long before it integrates viral DNA into human genomes.
While integrase was already known for helping HIV insert its genetic material into human DNA, the new study shows that integrase also forms filament-like structures inside the virus’s protective shell, known as the capsid. Using high-resolution cryo-electron microscopy (cryo-EM), the team found that these integrase filaments line the interior of the capsid, anchoring the viral RNA genome to the capsid walls in a zipper-like fashion and organizing it as the virus matures. Without these anchor structures, the virus cannot effectively package its RNA, rendering it non-infective.
The capsid is an extremely small and delicate structure — roughly 120 nanometers wide — that shields the virus and its genetic material. To visualize its inner architecture, the researchers combined advanced cryo-EM imaging at the Francis Crick Institute with molecular modeling and high-performance computing to build detailed 3D models showing how integrase interacts with both the capsid and viral RNA at an atomic level.
Previously, specialized inhibitors called ALLINIs were used to disrupt larger assemblies of integrase proteins, but these were not specifically targeting the integrase’s capsid-anchoring role. The new findings highlight that no existing U.S. Food and Drug Administration (FDA)-approved drugs currently target this structural function of integrase — suggesting a promising new pathway for antiviral drug development aimed at blocking HIV replication at a stage before DNA integration.
The study represents a large collaborative effort, involving researchers from institutions including the Francis Crick Institute, Harvard University, University of Oxford, Birkbeck College, and others. Professor Perilla emphasized the importance of sustained public funding from agencies like the U.S. National Science Foundation, National Institutes of Health, and Department of Energy in enabling this breakthrough research.
The full research findings were published in the journal Nature on February 18, 2026, under the title “Integrase anchors viral RNA to the HIV-1 capsid interior,” marking a significant advance in our understanding of HIV biology and potential routes to next-generation therapies.
