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Abstract
Natural products are the important source for the discovery of more potent anti-HIV agents. In this study, six daphnane diterpenoids including three unreported structures were isolated from Trigonostemon lii, which showed significant activities against HIV-1 strains replication in the nanomolar/picomolar range. Meanwhile, these diterpenoids significantly inhibited the fusion of H9/HIV-1 IIIB cells with uninfected C8166 cells, with the EC50s from 1.06 to 8.73 ng/mL, and did not show any inhibition activities against HIV-1 reverse transcriptase. Moreover, all of the diterpenoids shows significant inhibitions against T20-resistan HIV-1 strains, PNL4-3gp41(36G)V38E, N42S and pNL4-3gp41(36G)V38A, N42T. The results revealed that the six diterpenoids could be a new type of potential lead candidate as an HIV entry inhibitor, particularly for those infected by T20-resistant variants.
Graphic Abstract
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1 Kunming Institute of Botany, Chinese Academy of Sciences, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming, People’s Republic of China (GRID:grid.458460.b) (ISNI:0000 0004 1764 155X); Guizhou Minzu University, School of Ethnic Medicine, Guiyang, People’s Republic of China (GRID:grid.443389.1)
2 Kunming Institute of Botany, Chinese Academy of Sciences, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming, People’s Republic of China (GRID:grid.458460.b) (ISNI:0000 0004 1764 155X); Shanxi University, Institute of Molecular Science, Taiyuan, People’s Republic of China (GRID:grid.163032.5) (ISNI:0000 0004 1760 2008)
3 Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming, People’s Republic of China (GRID:grid.419010.d) (ISNI:0000 0004 1792 7072); Kunming Medical University, School of Basic Medical, Kunming, People’s Republic of China (GRID:grid.285847.4) (ISNI:0000 0000 9588 0960)
4 Kunming Institute of Botany, Chinese Academy of Sciences, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming, People’s Republic of China (GRID:grid.458460.b) (ISNI:0000 0004 1764 155X)
5 Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Center for Biosafety Mega-Science, Kunming, People’s Republic of China (GRID:grid.419010.d) (ISNI:0000 0004 1792 7072)