Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design.
Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design.
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DOI：
10.1038/srep13194
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发表时间：
2015-08-26
影响因子：
4.6
通讯作者：
Shimizu K
中科院分区：
文献类型：
--
作者：
Zhu Q;Bang TH;Ohnuki K;Sawai T;Sawai K;Shimizu K
神经氨酸酶（NA）抑制剂是临床上治疗流感的主要抗病毒药物。耐药性的增加使得发现新的NA抑制剂成为高度优先事项。通过体外NA抑制试验，对灵芝中的31种三萜类化合物进行了分析，发现灵芝酸T-Q和TR是H5 N1和H1N1 NA的两种抑制剂。构效关系研究表明，相应的三萜结构是一个潜在的支架NA抑制剂的设计。使用这些三萜类化合物作为探针，我们发现，通过进一步的计算机对接和相互作用分析，与氨基酸残基Arg 292和/或Glu 119的NA的相互作用是至关重要的H5 N1和H1N1的抑制。这些发现应该证明是有价值的NA抑制剂的设计和开发。
Neuraminidase (NA) inhibitors are the dominant antiviral drugs for treating influenza in the clinic. Increasing prevalence of drug resistance makes the discovery of new NA inhibitors a high priority. Thirty-one triterpenoids from the medicinal mushroom Ganoderma lingzhi were analyzed in an in vitro NA inhibition assay, leading to the discovery of ganoderic acid T-Q and TR as two inhibitors of H5N1 and H1N1 NAs. Structure-activity relationship studies revealed that the corresponding triterpenoid structure is a potential scaffold for the design of NA inhibitors. Using these triterpenoids as probes we found, through further in silico docking and interaction analysis, that interactions with the amino-acid residues Arg292 and/or Glu119 of NA are critical for the inhibition of H5N1 and H1N1. These findings should prove valuable for the design and development of NA inhibitors.