多甲酸抑制非洲猪瘟病毒聚合酶活性:机器学习和体外试验的发现
Jiwon Choi1, Hyundo Lee2, Soyoung Cho2
1College of Pharmacy, Dongduk Women's University, Seoul, 02748, Republic of Korea. edccjw@gmail.com.
Journal of computer-aided molecular design
|July 15, 2023
概括
非洲猪瘟病毒 (ASFV) 对全球粮食安全构成重大威胁. 这项研究确定了天然产品,如多酸,作为潜在的针对ASFV聚合酶的抗病毒药物,为治疗提供了新的希望.
科学领域:
- 病毒学和分子生物学
- 药物发现和天然产品化学化学
背景情况:
- 非洲猪瘟病毒 (ASFV) 在猪中引起一种高度传染性和致命的出血性疾病,导致严重的经济损失并影响全球粮食安全.
- 尽管它有影响,但目前没有商业上可用的ASFV疫苗或治疗方法,迫切需要对新型抗病毒疗法进行紧急研究.
- 之前的研究使用计算方法确定了像五星素,康格罗尔和福斯塔马提尼布这样的小分子作为潜在的ASFV抑制剂.
研究的目的:
- 识别具有高亲和力与ASFV聚合酶蛋白 (AsfvPolX) 的新型天然产品 (NP) 作为潜在的抗病毒剂.
- 从天然产品数据库中开发和提出一种有效的计算协议,用于从天然产品数据库中发现抗病毒药物.
主要方法:
- 采用机器学习算法与分子对接模拟相结合,以选天然产品数据库.
- 专注于识别结构上与已知的抗ASFV黄类药物相似的NP.
- 选择了五种有前途的天然产品进行进一步的研究,基于它们对AsfvPolX.的预测结合亲和力.
主要成果:
- 确定了几种天然产品,对ASFV聚合酶蛋白具有很高的亲和力.
- 在实验室中,多甲酸在剂量上显著抑制了AsfvPolX聚合酶活性.
- 该研究成功验证了用于识别潜在抗病毒天然产品的计算方法.
结论:
- 自然产品,特别是聚酸,显示出对抗非洲猪瘟病毒的新型治疗剂的希望.
- 拟议的计算策略为从自然产品库中发现新的抗病毒药物提供了一个有效的途径.
- 需要进一步的研究和开发,以推动这些发现成为ASFV的有效治疗方法.
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