Back to Browse Journals » International Journal of Nanomedicine » Volume 7

Cascade search for HSV-1 combinatorial drugs with high antiviral efficacy and low toxicity

Authors Ding X, Sanchez DJ, Shahangian A, Al-Shyoukh I, Cheng G, Ho CM

Published Date May 2012 Volume 2012:7 Pages 2281—2292

DOI http://dx.doi.org/10.2147/IJN.S27540

Received 22 October 2011, Accepted 3 March 2012, Published 10 May 2012

Xianting Ding1, David Jesse Sanchez2,3, Arash Shahangian2, Ibrahim Al-Shyoukh1,4, Genhong Cheng2, Chih-Ming Ho1

1Department of Mechanical and Aerospace Engineering, UCLA, Los Angeles, CA, USA; 2Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA; 4Molecular and Medical Pharmacology Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

Background: Infectious diseases cause many molecular assemblies and pathways within cellular signaling networks to function aberrantly. The most effective way to treat complex, diseased cellular networks is to apply multiple drugs that attack the problem from many fronts. However, determining the optimal combination of several drugs at specific dosages to reach an endpoint objective is a daunting task.
Methods: In this study, we applied an experimental feedback system control (FSC) method and rapidly identified optimal drug combinations that inhibit herpes simplex virus-1 infection, by only testing less than 0.1% of the total possible drug combinations.
Results: Using antiviral efficacy as the criterion, FSC quickly identified a highly efficacious drug cocktail. This cocktail contained high dose ribavirin. Ribavirin, while being an effective antiviral drug, often induces toxic side effects that are not desirable in a therapeutic drug combination. To screen for less toxic drug combinations, we applied a second FSC search in cascade and used both high antiviral efficacy and low toxicity as criteria. Surprisingly, the new drug combination eliminated the need for ribavirin, but still blocked viral infection in nearly 100% of cases.
Conclusion: This cascade search provides a versatile platform for rapid discovery of new drug combinations that satisfy multiple criteria.

Keywords: drug combination, HSV-1, combinatorial drug optimization, feedback system control, FSC, drug screening

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions

Shin YC, Yang WJ, Lee JH, Oh JW, Kim TW, Park JC, Hyon SH, Han DW

International Journal of Nanomedicine 2014, 9:4067-4078

Published Date: 22 August 2014

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Deng L, Zhang Y, Ma L, Jing X, Ke X, Lian J, Zhao Q, Yan B, Zhang J, Yao J, Chen J

International Journal of Nanomedicine 2013, 8:3271-3283

Published Date: 26 August 2013

Dendrimers functionalized with membrane-interacting peptides for viral inhibition

Tarallo R, Carberry TP, Falanga A, Vitiello M, Galdiero S, Galdiero M, Weck M

International Journal of Nanomedicine 2013, 8:521-534

Published Date: 5 February 2013

Controlled gentamicin release from multi-layered electrospun nanofibrous structures of various thicknesses

Sirc J, Kubinova S, Hobzova R, Stranska D, Kozlik P, Bosakova Z, Marekova D, Holan V, Sykova E, Michalek J

International Journal of Nanomedicine 2012, 7:5315-5325

Published Date: 8 October 2012

Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

Wang K, Zhang T, Liu L, Wang XL, Wu P, Chen ZG, Ni C, Zhang JS, Hu FQ, Huang J

International Journal of Nanomedicine 2012, 7:4487-4497

Published Date: 13 August 2012

Cationized dextran nanoparticle-encapsulated CXCR4-siRNA enhanced correlation between CXCR4 expression and serum alkaline phosphatase in a mouse model of colorectal cancer

Abedini F, Hosseinkhani H, Ismail M, Domb AJ, Omar AR, Chong PP, Hong PD, Yu DS, Farber IY

International Journal of Nanomedicine 2012, 7:4159-4168

Published Date: 31 July 2012

Development of a reduction-sensitive diselenide-conjugated oligoethylenimine nanoparticulate system as a gene carrier

Cheng G, He Y, Xie L, Nie Y, He B, Zhang Z, Gu Z

International Journal of Nanomedicine 2012, 7:3991-4006

Published Date: 31 July 2012

Nanofiber composites containing N-heterocyclic carbene complexes with antimicrobial activity

Elzatahry AA, Al-Enizi AM, Elsayed EA, Butorac RR, Al-Deyab SS, Wadaan MAM, Cowley AH

International Journal of Nanomedicine 2012, 7:2829-2832

Published Date: 7 June 2012

Servant leadership: a case study of a Canadian health care innovator

Vanderpyl TH

Journal of Healthcare Leadership 2012, 4:9-16

Published Date: 16 February 2012