Development of sulphated and naphthylsulphonated carbosilane dendrimers as topical microbicides to prevent HIV-1 sexual transmission

Córdoba, Enrique Vacas; Arnáiz, Eduardo; Relloso, Miguel; Sánchez-Torres, Carlos; García, Féderico; Pérez-Álvarez, Lucı́a; Gómez, Rafael; Mata, F. Javier de la; Pion, Marjorie; Muñoz‐Fernández, María Ángeles

doi:10.1097/qad.0b013e32835f2b7a

Cited by 51 publications

(46 citation statements)

References 38 publications

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“…17 Briefly, prechilled Vero cell monolayers in 24-well plates (175×10 3 cells/well) were treated with dendrimers for 1 hour at 4°C and infected with 150 PFU/well HSV-2 for 2 hours at 4°C. Cells were washed with cold 2% FBS/DMEM to remove unattached dendrimers and unabsorbed HSV-2 and overlaid with medium containing human Ig.…”

Section: Attachment Assaymentioning

confidence: 99%

“…Previously, we showed that both dendrimers did not induce vaginal irritation or inflammation in BALB/c mice and they were well tolerated for topical application. 8,17,31 Female BALB/c mice (20±2 g) that were 6-8 weeks old were housed at the CBMSO. Animal studies were conducted and approved by the CBMSO Institutional Animal Care and Use Committee (CEEA-CBMSO, Madrid, Spain).…”

Section: In Vivo Vaginal Challenge Assaymentioning

confidence: 99%

“…[7][8][9]17 However, their ability to inhibit other sexually transmitted infections is unknown. In this work, antiviral activity against HSV-2 of eight dendrimers, which previously showed high anti-HIV activity were researched.…”

Section: Screening Of Polyanionic Carbosilane Dendrimers Antiviral Acmentioning

confidence: 99%

“…8,14,15,17 The effect of polyanionic dendrimers in HSV-2 binding was studied ( Figure 3B). The attachment of HSV-2 to Vero cells was inhibited in a doseresponse effect by the three dendrimers ( Figure 3B).…”

mentioning

confidence: 99%

“…8,14,17,36 We performed a screening of eight selected polyanionic dendrimers that previously demonstrated anti-HIV-1 activity in vitro and in vivo 11 to select proper candidates for the development of a topical microbicide against HSV-2 infection. Plaque reduction assay showed that G1-S4, G2-S16, and G3-S16 have strong antiviral activity against HSV-2 in vitro by inhibiting HSV-2 binding and internalization into the Vero cells.…”

mentioning

confidence: 99%

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Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

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Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH–gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.

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Section: Attachment Assaymentioning

confidence: 99%

Section: In Vivo Vaginal Challenge Assaymentioning

confidence: 99%

Section: Screening Of Polyanionic Carbosilane Dendrimers Antiviral Acmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

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Dendronized Anionic Gold Nanoparticles: Synthesis, Characterization, and Antiviral Activity

Peña-González

García-Broncano

Ottaviani

et al. 2016

Chemistry A European J

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Anionic carbosilane dendrons decorated with sulfonate functions and one thiol moiety at the focal point have been used to synthesize water-soluble gold nanoparticles (AuNPs) through the direct reaction of dendrons, gold precursor, and reducing agent in water, and also through a place-exchange reaction. These nanoparticles have been characterized by NMR spectroscopy, TEM, thermogravimetric analysis, X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, elemental analysis, and zeta-potential measurements. The interacting ability of the anionic sulfonate functions was investigated by EPR spectroscopy with copper(II) as a probe. Different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups for complexation by copper(II). Toxicity assays of AuNPs showed that those produced through direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV-1 infection was higher in the case of dendronized AuNPs than in dendrons.

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A pilot study of the antiviral activity of anionic and cationic polyamidoamine dendrimers against the Middle East respiratory syndrome coronavirus

Kandeel

Al‐Taher

Kim

et al. 2020

Journal of Medical Virology

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The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that causes infection with a potentially fatal outcome. Dendrimers are highly branched molecules that can be added to antiviral preparations to improve their delivery, as well as their intrinsic antiviral activity. Studies on identifying anti-MERS-CoV agents are few. Three types of polyanionic dendrimers comprising the terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were used to assess their antiviral activity with the MERS-CoV plaque inhibition assay. The hydroxyl polyanionic set showed a 17.36% to 29.75% decrease in MERS-CoV plaque formation. The most potent inhibition of MERS-CoV plaque formation was seen by G (1.5)-16COONa (40.5% inhibition), followed by G(5)-128SA (39.77% inhibition). In contrast, the cationic dendrimers were cytotoxic to Vero cells. Polyanionic dendrimers can be added to antiviral preparations to improve the delivery of antivirals, as well as the intrinsic antiviral activity. K E Y W O R D S antiviral agents, cell cultures, coronavirus, research and analysis methods, virus classification

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Development of sulphated and naphthylsulphonated carbosilane dendrimers as topical microbicides to prevent HIV-1 sexual transmission

Abstract: These interesting results suggest that G3-S16 or G2-NF16 could be effective to inhibit HIV infection and transmission within genital mucosa as well as the spread of HIV transmission to human PBMC.

Cited by 51 publications

References 38 publications

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Dendronized Anionic Gold Nanoparticles: Synthesis, Characterization, and Antiviral Activity

A pilot study of the antiviral activity of anionic and cationic polyamidoamine dendrimers against the Middle East respiratory syndrome coronavirus

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