分析和机器学习方法识别了一种海星类固醇,它对COVID-19治疗开发具有有前途的活动
Mohamed S M Abd El Hafez1, Aya I Maiyza2, Hanan A Hassan2
1National Institute of Oceanography and Fisheries, NIOF, Cairo, Egypt. mohamedsaid80@yahoo.com.
来自海星Acanthaster planci的一种新型类固醇化合物,5α-cholesta-9(11)-en-3β,20β-diol,显示出显著的抗SARS-CoV-2活性. 这种天然产品表现出有希望的抗病毒潜力和有利的安全性,支持其作为COVID-19治疗药物的发展.
科学领域:
- 海洋天然产品 化学 化学
- 抗病毒药物发现发现
- 计算化学计算化学
背景情况:
- 迫切需要有效的COVID-19治疗方法,推动对天然产品的研究.
- 海洋生物是具有治疗潜力的生物活性化合物的丰富来源.
研究的目的:
- 从Acanthaster planci.中分离和描述一种生物活性类固醇化合物.
- 评估隔离化合物的抗SARS-CoV-2活性和安全概况.
- 开发用于预测抗病毒活性和简化药物发现的计算工具.
主要方法:
- 使用HREIMS,FTIR和NMR光谱学对类固醇化合物的隔离和结构阐明.
- 在体外减少斑块的测试以确定抗SARS-CoV-2活性 (IC50).
- 对关键病毒点 (Mpro,NSP10,RNA依赖RNA聚合酶) 的分子对接研究.
- 在 silico ADMET 分析和毒性评估.
- 机器学习模型开发 (XGBoost) 用于IC50预测和Web应用程序创建.
主要成果:
- 从Acanthaster planci.中分离了5α-cholesta-9(11) -en-3β,20β-diol (C27H46O2) 的离合物.
- 证明了显著的SARS-CoV-2抑制 (85%在5 ng/μl,IC50 = 5.86 μM).
- 对病毒点Mpro,NSP10和RNA依赖RNA聚合酶的高结合亲缘关系.
- 在中有利的药理动力学和毒性概况 (高BBB透率,非肝毒性,低刺激性).
- 开发了一种可靠的机器学习模型来预测IC50值,并得到ENHPCG的验证.
结论:
- 5α-cholesta-9(11)-en-3β,20β-diol是一种强大的SARS-CoV-2抑制剂,具有有前途的安全性.
- 包括机器学习在内的计算方法有效地支持和加速抗病毒药物发现.
- 这种来自海洋的类固醇化合物代表了针对COVID-19的进一步药理发展的潜在候选人.
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