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<p>Lenacapavir is a first-in-class, long-acting HIV-1 capsid inhibitor and represents a significant advancement in both the treatment and prevention of HIV-1 infection. It is highly effective against both wild-type and multidrug-resistant strains of the virus. It has a unique mechanism of action involving the disruption of HIV-1 capsid assembly and nuclear import, which ultimately prevents the virus from integrating its genetic material into the host cell’s DNA and hinders viral replication. This review covers lenacapavir’s discovery and development, with a focus on its target validation, lead optimization, chemical synthesis, pharmacokinetic properties, safety profile, and clinical applications.</p><p></p>

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Lenacapavir, a first-in-class, long-acting capsid inhibitor approved for both HIV-1 treatment and prevention

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月31日

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  • Zi Hui,
  • Xiang-Yang Ye,
  • Yuting Zhang,
  • Longqin Hu,
  • Tian Xie,
  • Zhao-Qian Liu

摘要

Lenacapavir is a first-in-class, long-acting HIV-1 capsid inhibitor and represents a significant advancement in both the treatment and prevention of HIV-1 infection. It is highly effective against both wild-type and multidrug-resistant strains of the virus. It has a unique mechanism of action involving the disruption of HIV-1 capsid assembly and nuclear import, which ultimately prevents the virus from integrating its genetic material into the host cell’s DNA and hinders viral replication. This review covers lenacapavir’s discovery and development, with a focus on its target validation, lead optimization, chemical synthesis, pharmacokinetic properties, safety profile, and clinical applications.