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人类SERPINs的宿主细胞和病毒蛋白酶标通过in silico对接确定

Joaquin Rodriguez Galvan¹, Maren de Vries¹, Shiraz Belblidia¹

¹New York University Grossman School of Medicine, Microbiology Department, New York, NY, USA.

The EMBO journal

|September 9, 2025

概括

人类血清蛋白酶抑制剂 (SERPINs) 在呼吸系统病毒感染期间得到广泛表达. PAI-1和PAI-2 SERPIN分别抑制了SARS-CoV-2和腺病毒,提供了潜在的治疗点.

科学领域:

病毒学病毒学
生物化学生物化学
免疫学免疫学免疫学

背景情况:

血清蛋白酶抑制剂 (SERPINs) 调节生理过程,但它们在病毒感染中的作用尚不清楚.
了解感染期间的SERPIN表达和点对于确定治疗策略至关重要.

研究的目的:

为了研究呼吸道病毒感染期间人类SERPINs的表达.
为了确定SERPINs与病毒或宿主蛋白酶之间的新型相互作用.
评估针对SARS-CoV-2和腺病毒的特定SERPIN的抗病毒潜力.

主要方法:

从COVID-19患者和人类呼吸道上皮培养物 bronchioalveolar lavages 中分析SERPIN表达.
在10个SERPIN与48个宿主蛋白酶的化分子对接中.
蛋白酶活性测定用于验证预测的SERPIN-蛋白酶相互作用.
在体外测试以评估SERPINs对病毒复制和传染性的影响.

主要成果:

人类SERPINs的广泛表达在对呼吸道病毒感染的反应中被观察到.
在接中预测了新的SERPIN-蛋白酶相互作用,并验证了PAI-1 (SERPINE1) 和PAI-2 (SERPINB2) 的相互作用.
发现PAI-1抑制了对SARS-CoV-2成熟至关重要的cathepsin L,抑制了WA-1和Omicron BA.1变种的复制.
通过抑制其蛋白酶,PAI-2显示出对人类腺病毒5的抗病毒活性.

结论:

人类SERPIN在呼吸道病毒感染期间升级,这表明它在宿主防御中起着重要作用.
PAI-1和PAI-2分别对SARS-CoV-2和腺病毒表现出直接的抗病毒活性.
这些发现凸显了SERPINs作为治疗病毒病原体的治疗干预的有希望的候选人.

关键词:

亚地诺病毒蛋白酶是什么?猫头陷入了其中.血原激活剂抑制剂1 抑制剂1 血原激活剂抑制剂2 抑制剂这就是TMPRSS.

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