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化学蛋白质学方法用于选与SARS-Cov-2共价结合的小分子抑制剂

Liuhai Zheng^1,2, Qian Zhang³, Piao Luo³

¹Department of Pulmonary and Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Institute of Respiratory Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.

Advanced biology

|October 16, 2024

概括

人工智能和基于活动的蛋白质分析快速识别了针对SARS-CoV-2 Omicron变体的小分子. 美国食品和药物管理局批准的药物酸证明了强大的中和作用,验证了一个新的药物发现平台.

科学领域:

药物的发现和开发.
病毒学病毒学
计算生物学是一种计算生物学.

背景情况:

SARS-CoV-2 的快速传播和演变,特别是 Omicron 变种,需要新的治疗策略.
目前的单克隆抗体治疗对新出现的SARS-CoV-2变种的有效性较低,迫切需要新的抗病毒药物.
开发广泛的治疗方法对于对抗当前和未来的SARS-CoV-2菌株和重组剂至关重要.

研究的目的:

快速识别能够对 SARS-CoV-2 Omicron 变种的受体结合域 (RBD) 进行协同结合的小分子药物.
建立和验证一个全面的平台,整合人工智能 (AI),基于活动的蛋白质分析 (ABPP) 和生化分析,以加速药物发现.
评估已识别的候选药物对Omicron变种的中和效力.

主要方法:

人工智能 (AI) 和基于活动的蛋白质分析 (ABPP) 的联合应用,用于小分子的高通量选.
表面等离子体共振 (SPR) 测试以确认小分子与RBD的结合动力学和亲和力.
伪病毒中和实验,以评估候选药物的抗病毒疗效.
分子对接模拟用于预测结合相互作用.

主要成果:

人工智能和ABPP成功地确定了具有与Omicron RBD结合的潜力的小分子.
美国食品和药物管理局 (FDA) 批准的药物酸对Omicron伪病毒具有显著的中和作用,IC50为23.56 × 10−6m.
综合平台在快速识别和评估潜在的抗SARS-CoV-2小分子药物方面表现出有效性.

结论:

一个结合人工智能,生物化学分析,SPR,分子对接和伪病毒查的新平台,能够快速识别和验证抗SARS-CoV-2小分子药物.
酸代表了一个有前途的治疗候选人,具有强大的中和活性,可以对抗Omicron变种.
这种方法为发现针对当前和新出现的SARS-CoV-2变种的治疗方法提供了经过验证的策略.

关键词:

这是ABPPPP ABPPPP.在这里,我们可以看到AIAIAI.这就是Omicron.在SARS-CoV-2中.具有共价结合的结合.

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