ArticlePloS one2013
Polyanionic candidate microbicides accelerate the formation of semen-derived amyloid fibrils to enhance HIV-1 infection.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- In Vitro Antiviral Activity of Red Algae Extracts fromTropical medicine and infectious disease · 2026Article
- Review
- A Brief History and Advancement of Contraceptive Multipurpose Prevention Technology (cMPT) Products.Open access journal of contraception · 2023Review
- Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays.Andrology · 2022Article
- Carrageenans as Broad-Spectrum Microbicides: Current Status and Challenges.Marine drugs · 2020Review
- Development of multipurpose technologies products for pregnancy and STI prevention: update on polyphenylene carboxymethylene MPT gel development†.Biology of reproduction · 2020Article
- The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans.Journal of virology · 2020Article
- Tolcapone Potently Inhibits Seminal Amyloid Fibrils Formation and Blocks Entry of Ebola Pseudoviruses.Frontiers in microbiology · 2020Article
- Impact of semen-derived amyloid (SEVI) on sperm viability and motility: its implication in male reproductive fitness.European biophysics journal : EBJ · 2019Article
- The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1.The Journal of biological chemistry · 2019Article
- Inhibitory Effect of Naphthoquinone-Tryptophan Hybrid towards Aggregation of PAP f39 Semen Amyloid.Molecules (Basel, Switzerland) · 2018Article
- [PSB0739 inhibits formation of semen-derived amyloid fibril].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity.Retrovirology · 2018Article
- Structure, function and antagonism of semen amyloids.Chemical communications (Cambridge, England) · 2018Review
- Sulfonated Compounds Bind with Prostatic Acid Phosphatase (PAPChemistryOpen · 2018Article
- 3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor.Frontiers in microbiology · 2018Article
- An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques.Drug delivery and translational research · 2017Article
- Epigallocatechin Gallate Inhibits Macaque SEVI-Mediated Enhancement of SIV or SHIV Infection.Journal of acquired immune deficiency syndromes (1999) · 2017Article
- Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.Drug design, development and therapy · 2017Review
- CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyanionic candidate microbicides, including cellulose sulfate, carrageenan, PRO 2000, were proven ineffective in preventing HIV-1 transmission and even cellulose sulfate showed increased risk of HIV acquisition in the Phase III efficacy trials. Semen plays critical roles in HIV-1 sexual transmission. Specifically, amyloid fibrils formed by fragments of prostatic acidic phosphatase (PAP) in semen termed semen-derived enhancer of virus infection (SEVI) could drastically enhance HIV-1 infection. Here we investigated the interaction between polyanions and PAP248-286, a prototype peptide of SEVI, to understand the possible cause of polyanionic candidate microbicides to fail in clinical trials. We found anionic polymers could efficiently promote SEVI fibril formation, most likely mediated by the natural electrostatic interaction between polyanions and PAP248-286, as revealed by acid native PAGE and Western blot. The overall anti-HIV-1 activity of polyanions in the presence or absence of PAP248-286 or semen was evaluated. In the viral infection assay, the supernatants of polyanions/PAP248-286 or polyanions/semen mixtures containing the free, unbound polyanionic molecules showed a general reduction in antiviral efficacy, while the pellets containing amyloid fibrils formed by the polyanion-bound PAP248-286 showed aggravated enhancement of viral infection. Collectively, from the point of drug-host protein interaction, our study revealed that polyanions facilitate SEVI fibril formation to promote HIV-1 infection, thus highlighting a molecular mechanism underlying the failure of polyanions in clinical trials and the importance of drug-semen interaction in evaluating the anti-HIV-1 efficacy of candidate microbicides.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.