对Ibuzatrelvir对SARS-CoV-2循环变种和体外耐药性突变的活性进行分析
Irina Yurgelonis1, Devendra K Rai2, Zhenghui Li3
1Anti-Infectives, Pfizer Research and Development, Pfizer Inc, Pearl River, NY 10965, USA.
Antiviral research
|February 1, 2026
概括
一种新型的SARS-CoV-2 Mpro抑制剂Ibuzatrelvir显示出对主要变异的持续抗病毒疗效. 抗性突变很少见,支持其持续的临床评估来治疗COVID-19.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 传染性疾病 传染性疾病
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 继续演变,需要新的抗病毒治疗.
- 伊布扎特雷尔维尔是一种第二代SARS-CoV-2主要蛋白酶 (Mpro) 抑制剂,具有强大的抗病毒活性,独立于药理动力学增强剂.
研究的目的:
- 评估伊布扎特雷尔维尔对当前SARS-CoV-2变种的抗病毒疗效.
- 描述伊布扎特雷尔维尔体外耐药性概况,并确定与耐药性相关的潜在突变.
主要方法:
- 针对SARS-CoV-2主要变种 (alpha 到 omicron) 的ibuzatrelvir抗病毒活性测试.
- 在药物压力下的病毒突变体体内选择以确定Mpro.中的耐药性相关氨基酸替代物.
- 与其他抗病毒药物进行交叉耐药性测试.
主要成果:
- 伊布扎特雷尔维尔在2020-2024年期间对所有主要的SARS-CoV-2变种保持了抗病毒疗效.
- 发现的关键抗性相关的Mpro替代物包括T21I,L232R,S144A,以及E166V+L232R等组合.
- E166V+L232R双替代赋予了最高的耐药性,但在监测数据中患病率非常低.
- 交叉耐药性测试显示保留了对remdesivir的敏感性,但对nirmatrelvir的耐药性;对抗抗Ensitrelvir耐药的M49L突变物保持了活性.
结论:
- 伊布扎特雷尔维尔证明了对循环的SARS-CoV-2变种的持续有效性.
- 关键耐药性突变的低患病率支持伊布扎特雷尔病毒的持续发展.
- 伊布扎特雷尔维尔代表了COVID-19治疗的有希望的治疗候选者.
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