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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
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TitleLignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission
 
AuthorsQiu, M2
Wang, Q2
Chu, Y2
Yuan, Z2
Song, H2
Chen, Z1
Wu, Z2
 
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
 
CitationPLoS One, 2012, v. 7 n. 4, article no. e35906 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0035906
 
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.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0035906
 
PubMed Central IDPMC3338758
 
ISI Accession Number IDWOS:000305336000082
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorQiu, M
 
dc.contributor.authorWang, Q
 
dc.contributor.authorChu, Y
 
dc.contributor.authorYuan, Z
 
dc.contributor.authorSong, H
 
dc.contributor.authorChen, Z
 
dc.contributor.authorWu, Z
 
dc.date.accessioned2012-08-08T08:52:18Z
 
dc.date.available2012-08-08T08:52:18Z
 
dc.date.issued2012
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPLoS One, 2012, v. 7 n. 4, article no. e35906 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0035906
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0035906
 
dc.identifier.hkuros206329
 
dc.identifier.isiWOS:000305336000082
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.

 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue4, article no. e35906
 
dc.identifier.pmcidPMC3338758
 
dc.identifier.pmid22558266
 
dc.identifier.scopuseid_2-s2.0-84860476702
 
dc.identifier.urihttp://hdl.handle.net/10722/157692
 
dc.identifier.volume7
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS One
 
dc.relation.referencesReferences in Scopus
 
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 transmission
 
dc.typeArticle
 
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<contributor.author>Yuan, Z</contributor.author>
<contributor.author>Song, H</contributor.author>
<contributor.author>Chen, Z</contributor.author>
<contributor.author>Wu, Z</contributor.author>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Nanjing University