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Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design.

ABSTRACT: 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.

SUBMITTER: Zhu Q

PROVIDER: S-EPMC4549708 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design.

Zhu Qinchang Q Bang Tran Hai TH Ohnuki Koichiro K Sawai Takashi T Sawai Ken K Shimizu Kuniyoshi K

Scientific reports 20150826

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 ...[more]

PMID: 26307417

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