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针对SARS-CoV-2 RBD/hACE2相互作用的潜在阻断的研究

Sara M Villada-Troncoso¹, Jenny Andrea Arévalo-Romero^1,2, Vanessa Hernández Rivera³

¹Institute for the Study in Inborn Errors of Metabolism-IEIM, Faculty of Science, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Pharmaceuticals (Basel, Switzerland)

|September 28, 2024

概括

研究人员通过实验验证了三种 (BP2,BP9,BP11) 阻止SARS-CoV-2尖端蛋白与人体细胞结合. 酸BP2表现出最强大的抗病毒活性,显示出新的COVID-19治疗方法的前景.

科学领域:

病毒学病毒学
生物技术是生物技术.
药物发现药物发现药物发现

背景情况:

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,由于新出现的变种,需要新的治疗方法.
病毒通过尖端蛋白的受体结合域 (RBD) 进入细胞,与人体血管素转化酶2 (ACE2) 结合.
之前的in silico研究确定了类BP2,BP9和BP11作为RBD-ACE2相互作用的潜在破坏者.

研究的目的:

实验验证类BP2,BP9和BP11在抑制SARS-CoV-2 RBD-ACE2相互作用中的有效性.
评估这些的生产产量和结合能力与各种RBD变体相比.
确定针对SARS-CoV-2的治疗开发最有前途的.

主要方法:

在酵母 Komagataella phaffii 中,复合生成的质BP2,BP9和BP11.
在实验室中评估活性,使用具有多个RBD变异的结合试验.
评估RBD-ACE2相互作用的抑制,并确定IC50值.

主要成果:

酸BP2,BP9和BP11已成功生产,产量分别为14.34,4.01,1.35毫克/升.
这三种都表现出来自SARS-CoV-2变异的RBD的相互作用,BP2显示出优越的识别能力.
这些抑制了RBD/hACE2相互作用,IC50值在1.03至5.35nm之间,BP2是最有效的.

结论:

酸BP2作为开发针对SARS-CoV-2的新型干预措施的治疗候选者,显示出显著的前景.
这些发现支持BP2和相关在向利用haCE2进入细胞的冠状病毒方面的潜力.
实验验证证证实了in silico预测,为进一步的药物开发工作铺平了道路.

关键词:

在 COVID-19 疫情中,科玛格塔贝拉 (Komagataella phaffii) 是一个有趣的植物.其他RBD变体这就是SARS-CoV-2病毒.阻断可以阻断.

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