Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue virus

被引：8

作者：

Amraiz, Deeba ^{[1
]}

Zaidi, Najam-us-Sahar Sadaf ^{[1
]}

Fatima, Munazza ^{[1
]}

机构：

[1] Natl Univ Sci & Technol, Atta Ur Rahman Sch Appl Biosci, Sect H-12, Islamabad 44000, Pakistan

来源：

TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH | 2017年 / 16卷 / 05期

关键词：

Dengue virus replication; Hsp90; Gedunin; Antiviral; Molecular docking; SHOCK-PROTEIN; 90; MOLECULAR CHAPERONE HSP90; CLINICAL DEVELOPMENT; CELLULAR CHAPERONE; REPLICATION; CELLS; HEAT-SHOCK-PROTEIN-90; IDENTIFICATION; MACHINERY; INFECTION;

D O I：

10.4314/tjpr.v16i5.5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Purpose: To evaluate the antiviral potential of a tetranortriterpenoid, gedunin, against dengue virus (DENV) replication by targeting the host chaperone, Hsp90. Methods: The compound, gedunin, was tested against the replication of DENV in vitro using BHK-15 cells transfected with DENV-2 subgenomic replicon. Molecular docking of gedunin with Hsp90 protein was performed for evaluation of mode of action, using the program, Autodock vina. Results: In vitro antiviral data showed that gedunin significantly (p < 0.05) reduced DENV replication with EC50 of 10 mu M. Further, in silico molecular docking data revealed strong interaction of gedunin with the ATP/ADP binding site of the host protein, Hsp90, with an estimated average free binding energy of - 8.9 kcal/mol. Conclusion: The results validate gedunin as a potential antiviral candidate. Further in vitro assays and in vivo viral challenge studies are required to confirm the exact mode of action and pharmacological profile of gedunin in DENV infections.

引用

页码：997 / 1004

页数：8

共 29 条

[1] Heat Shock Protein 90 as a Drug Target: Some Like It Hot [J].

Banerji, Udai .

CLINICAL CANCER RESEARCH, 2009, 15 (01) :9-14

[2] Gedunin, a Novel Hsp90 inhibitor: Semisynthesis of Derivatives and Preliminary Structure-Activity Relationships [J].

Brandt, Gary E. L. ;

Schmidt, Matthew D. ;

Prisinzano, Thomas E. ;

Blagg, Brian S. J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (20) :6495-6502

[3] Nuclear sequestration of cellular chaperone and proteasomal machinery during herpes simplex virus type 1 infection [J].

Burch, AD ;

Weller, SK .

JOURNAL OF VIROLOGY, 2004, 78 (13) :7175-7185

[4] Hsp90 inhibitors reduce influenza virus replication in cell culture [J].

Chase, Geoffrey ;

Deng, Tao ;

Fodor, Ervin ;

Leung, Bo Wah ;

Mayer, Daniel ;

Schwemmle, Martin ;

Brownlee, George .

VIROLOGY, 2008, 377 (02) :431-439

[5] Antiviral activity and RNA polyinerase degradation following Hsp90 inhibition in a range of negative strand viruses [J].

Connor, John H. ;

McKenzie, Margie O. ;

Parks, Griffith D. ;

Lyles, Douglas S. .

VIROLOGY, 2007, 362 (01) :109-119

[6]

Debjit Bhowmik Debjit Bhowmik, 2010, Journal of Chemical and Pharmaceutical Research, V2, P62

[7] Broad action of Hsp90 as a host chaperone required for viral replication [J].

Geller, Ron ;

Taguwa, Shuhei ;

Frydman, Judith .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (03) :698-706

[8] Molecular chaperone Hsp90 is important for vaccinia virus growth in cells [J].

Hung, JJ ;

Chung, CS ;

Chang, W .

JOURNAL OF VIROLOGY, 2002, 76 (03) :1379-1390

[9] Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers [J].

Jhaveri, Komal ;

Taldone, Tony ;

Modi, Shanu ;

Chiosis, Gabriela .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (03) :742-755

[10] Gedunin, a Novel Natural Substance, Inhibits Ovarian Cancer Cell Proliferation [J].

Kamath, Siddharth G. ;

Chen, Ning ;

Xiong, Yin ;

Wenham, Robert ;

Apte, Sachin ;

Humphrey, Marcia ;

Cragun, Janiel ;

Lancaster, Johnathan M. .

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2009, 19 (09) :1564-1569

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