莱纳卡巴维尔的发现:为HIV-1治疗和暴露前预防的第一级两年一次的囊抑制剂
Eda Canales1, Winston Tse1, Scott D Schroeder1
1Medicinal Chemistry, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, California 94404, United States.
Journal of medicinal chemistry
|October 1, 2025
概括
莱纳卡帕维尔是一种新的艾滋病毒囊抑制剂,提供强效,长效的治疗和预防. 这种突破性的抗病毒药物提供了一种独特的每年两次治疗方案,在妇女中实现100%的保护,并推进艾滋病毒流行病控制.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 药用化学 医学化学
背景情况:
- 人类免疫缺陷病毒 (HIV) 囊是其生命周期中必不可少的关键病毒成分.
- 针对艾滋病毒囊组装是抗病毒治疗干预的有希望的策略.
- 以前的努力集中在识别小分子来破坏囊单体相互作用.
研究的目的:
- 发现和开发一种新,强效和长效的HIV囊抑制剂.
- 确定有助于多阶段HIV囊抑制的复杂结构元素.
- 评估HIV-1治疗和预防开发的抑制剂的临床疗效.
主要方法:
- 2006年启动了选活动,以确定破坏囊蛋白与蛋白相互作用的小分子.
- 多年来复合设计和优化的多个周期.
- 临床试验评估候选药物lenacapavir的疗效和安全性.
主要成果:
- 发现了lenacapavir,一个强大的 (HIV-1 EC50 = 105 pM) 和长效的HIV抗病毒.
- 为lenacapavir开发一个独特的每年两次的剂量方案.
- 在HIV-1治疗和预防方面显示出强大的临床疗效,包括在女性中100%的保护.
结论:
- 莱纳卡帕维尔在HIV-1治疗和预防方面取得了重大进展.
- 该药物的独特剂量方案和高效率有可能对全球艾滋病毒流行病产生深远影响.
- 这项工作突显了针对艾滋病毒囊的多年药物设计战略的成功.
相关概念视频
Retrovirus Life Cycles
49.3K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
49.3K
Retroviruses
14.6K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
14.6K
Subviral Agents
525
Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
525


