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Lenacapavir, an innovative anti-retroviral drug approved by the European Union and the US FDA, disrupts HIV replication by targeting the virus’s protective capsid. Research from UNSW Sydney reveals its mechanism, offering insights for developing future antiviral therapies. Unlike existing treatments, Lenacapavir specifically destabilizes the HIV capsid, which encases the virus’s genetic material during its entry into host cells.
Led by Professor Till Böcking and Dr. David Jacques, the research team utilized cell infection studies and single-molecule imaging to understand how Lenacapavir interferes with the HIV lifecycle. Rather than strengthening the capsid, Lenacapavir’s action causes the capsid to become brittle and rupture prematurely, exposing the viral RNA to the hostile environment in host cells. Additionally, it disrupts the construction of new capsids by forcing errors, leading to faulty capsids that can’t protect the viral genome.
This study clarifies how capsid-targeting drugs function and highlights Lenacapavir’s superiority over other compounds. The findings provide a foundation for targeting other viruses with similar protective capsid structures, potentially advancing antiviral drug development. The research is published in the journal eLife and funded by various health organizations.
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