Article
Structural and mechanistic bases for resistance of the M66I capsid variant to lenacapavir.
mBio - 14 May 2025
Briganti Lorenzo, Annamalai Arun S, Bester Stephanie M, Wei Guochao, Andino-Moncada Jonathan R, Singh Satya P, Kleinpeter Alex B, Tripathi Meghna, Nguyen Binh, Radhakrishnan Rajalingam, Singh Parmit K, Greenwood Juliet, Schope Lauren I, Haney Reed, Huang Szu-Wei, Freed Eric O, Engelman Alan N, Francis Ashwanth C, Kvaratskhelia Mamuka
Abstract excerpt
Lenacapavir (LEN) is the first-in-class viral capsid protein (CA) targeting antiretroviral for treating multi-drug-resistant HIV-1 infection. Clinical trials and cell culture experiments have identified resistance-associated mutations (RAMs) in the vicinity of the hydrophobic CA pocket targeted by LEN. The M66I substitution conferred by far the highest level of resistance to the inhibitor compared to other RAMs....
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