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Article: Lignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission

TitleLignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission
Authors
KeywordsAntibody specificity
Antigen binding
Antiviral activity
Binding affinity
Binding site
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2012, v. 7 n. 4, article no. e35906 How to Cite?
Abstract
Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-kappaB activation and has no significant up-regulation of IL-1alpha/beta and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.
Persistent Identifierhttp://hdl.handle.net/10722/157692
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Science and Technology Major Project Grant2012ZX10001007-009-001
National Science Foundation of China30870124
International Collaborative Research Grant from the Ministry of Sciences and Technology of China2009DFA31260
Funding Information:

This study was supported by a National Science and Technology Major Project Grant (Grant No. 2012ZX10001007-009-001), and a grant from National Science Foundation of China (Grant No. 30870124) and an International Collaborative Research Grant from the Ministry of Sciences and Technology of China (Grant No. 2009DFA31260) (http://www.nsfc.gov.cn/Portal0/default152.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Nanjing University
DC FieldValueLanguage
dc.contributor.authorQiu, Men_US
dc.contributor.authorWang, Qen_US
dc.contributor.authorChu, Yen_US
dc.contributor.authorYuan, Zen_US
dc.contributor.authorSong, Hen_US
dc.contributor.authorChen, Zen_US
dc.contributor.authorWu, Zen_US
dc.date.accessioned2012-08-08T08:52:18Z-
dc.date.available2012-08-08T08:52:18Z-
dc.date.issued2012en_US
dc.identifier.citationPLoS One, 2012, v. 7 n. 4, article no. e35906en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/157692-
dc.description.abstractSome secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-kappaB activation and has no significant up-regulation of IL-1alpha/beta and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_US
dc.relation.ispartofPLoS Oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAntibody specificity-
dc.subjectAntigen binding-
dc.subjectAntiviral activity-
dc.subjectBinding affinity-
dc.subjectBinding site-
dc.titleLignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmissionen_US
dc.typeArticleen_US
dc.identifier.emailQiu, M: wzhw@nju.edu.cnen_US
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityChen, Z=rp00243en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0035906en_US
dc.identifier.pmid22558266-
dc.identifier.pmcidPMC3338758-
dc.identifier.scopuseid_2-s2.0-84860476702en_US
dc.identifier.hkuros206329-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860476702&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume7en_US
dc.identifier.issue4, article no. e35906en_US
dc.identifier.isiWOS:000305336000082-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWu, Z=55204054600en_US
dc.identifier.scopusauthoridChen, Z=35271180800en_US
dc.identifier.scopusauthoridSong, H=55203934600en_US
dc.identifier.scopusauthoridYuan, Z=55203720400en_US
dc.identifier.scopusauthoridChu, Y=55203385300en_US
dc.identifier.scopusauthoridWang, Q=35747402600en_US
dc.identifier.scopusauthoridQiu, M=55203251600en_US

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