Aureonitol, a Fungi-Derived Tetrahydrofuran, Inhibits Influenza Replication by Targeting Its Surface Glycoprotein Hemagglutinin

被引:21
作者
Sacramento, Carolina Q. [1 ,2 ,3 ]
Marttorelli, Andressa [1 ,2 ,3 ]
Fintelman-Rodrigues, Natalia [1 ,2 ,3 ]
de Freitas, Caroline S. [1 ,2 ,3 ]
de Melo, Gabrielle R. [1 ,2 ,3 ]
Rocha, Marco E. N. [1 ,2 ,3 ,4 ]
Kaiser, Carlos R. [5 ]
Rodrigues, Katia F. [6 ]
da Costa, Gisela L. [6 ]
Alves, Cristiane M. [1 ]
Santos-Filho, Osvaldo [1 ]
Barbosa, Jussara P. [6 ]
Souza, Thiago Moreno L. [1 ,2 ,3 ]
机构
[1] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Virus Resp, Rio De Janeiro, Brazil
[2] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Imunofarmacol, Rio De Janeiro, Brazil
[3] Fundacao Oswaldo Cruz, Ctr Desenvolvimento Tecnol Saude, Rio De Janeiro, Brazil
[4] Fundacao Oswaldo Cruz, Farmanguinhos, Lab Quim Prod Nat 5, Rio De Janeiro, Brazil
[5] Univ Fed Rio de Janeiro, Inst Quim, Rio De Janeiro, Brazil
[6] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Taxon Bioquim & Bioprospeccao Fungos, Rio De Janeiro, Brazil
来源
PLOS ONE | 2015年 / 10卷 / 10期
关键词
ALGA DICTYOTA-PFAFFII; CHAETOMIUM-GLOBOSUM; NEURAMINIDASE INHIBITORS; DOLABELLANE DITERPENE; VIRUS-INFECTION; HIV-1; PROTEASE; ACTIVE-SITE; DRUG; RESISTANT; ARBIDOL;
D O I
10.1371/journal.pone.0139236
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The influenza virus causes acute respiratory infections, leading to high morbidity and mortality in groups of patients at higher risk. Antiviral drugs represent the first line of defense against influenza, both for seasonal infections and pandemic outbreaks. Two main classes of drugs against influenza are in clinical use: M2-channel blockers and neuraminidase inhibitors. Nevertheless, because influenza strains that are resistant to these antivirals have been described, the search for novel compounds with different mechanisms of action is necessary. Here, we investigated the anti-influenza activity of a fungi-derived natural product, aureonitol. This compound inhibited influenza A and B virus replication. This compound was more effective against influenza A(H3N2), with an EC50 of 100 nM. Aureonitol cytoxicity was also very low, with a CC50 value of 1426 mu M. Aureonitol inhibited influenza hemagglutination and, consequently, significantly impaired virus adsorption. Molecular modeling studies revealed that aureonitol docked in the sialic acid binding site of hemagglutinin, forming hydrogen bonds with highly conserved residues. Altogether, our results indicate that the chemical structure of aureonitol is promising for future anti-influenza drug design.
引用
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页数:17
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