Article: Lignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission
| Title | Lignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission |
|---|---|
| Authors | Qiu, M2 Wang, Q2 Chu, Y2 Yuan, Z2 Song, H2 Chen, Z1 Wu, Z2 |
| Keywords | Antibody specificity Antigen binding Antiviral activity Binding affinity Binding site |
| Issue Date | 2012 |
| Publisher | Public 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?] DOI: http://dx.doi.org/10.1371/journal.pone.0035906 |
| 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. |
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 |
| DOI | http://dx.doi.org/10.1371/journal.pone.0035906 |
| PubMed Central ID | PMC3338758 |
| References | References in Scopus |
| dc.contributor.author | Qiu, M | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Wang, Q | ||||||||
| dc.contributor.author | Chu, Y | ||||||||
| dc.contributor.author | Yuan, Z | ||||||||
| dc.contributor.author | Song, H | ||||||||
| dc.contributor.author | Chen, Z | ||||||||
| dc.contributor.author | Wu, Z | ||||||||
| dc.date.accessioned | 2012-08-08T08:52:18Z | ||||||||
| dc.date.available | 2012-08-08T08:52:18Z | ||||||||
| dc.date.issued | 2012 | ||||||||
| dc.description.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. | ||||||||
| dc.description.nature | published_or_final_version | ||||||||
| dc.identifier.citation | PLoS One, 2012, v. 7 n. 4, article no. e35906 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0035906 | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0035906 | ||||||||
| dc.identifier.hkuros | 206329 | ||||||||
| dc.identifier.isi | WOS:000305336000082
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.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||||
| dc.identifier.issue | 4, article no. e35906 | ||||||||
| dc.identifier.pmcid | PMC3338758 | ||||||||
| dc.identifier.pmid | 22558266 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-84860476702 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/157692 | ||||||||
| dc.identifier.volume | 7 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||||
| dc.publisher.place | United States | ||||||||
| dc.relation.ispartof | PLoS One | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||||
| dc.subject | Antibody specificity | ||||||||
| dc.subject | Antigen binding | ||||||||
| dc.subject | Antiviral activity | ||||||||
| dc.subject | Binding affinity | ||||||||
| dc.subject | Binding site | ||||||||
| dc.title | Lignosulfonic acid exhibits broadly anti-HIV-1 activity: potential as a microbicide candidate for the prevention of HIV-1 sexual transmission | ||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- Nanjing University