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The AGMA1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice

Author:
Donalisio, Manuela, Quaranta, Paola, Chiuppesi, Flavia, Pistello, Mauro, Cagno, Valeria, Cavalli, Roberta, Volante, Marco, Bugatti, Antonella, Rusnati, Marco, Ranucci, Elisabetta, Ferruti, Paolo, Lembo, David
Source:
Biomaterials 2016 v.85 pp. 40-53
ISSN:
0142-9612
Subject:
HIV infections, Human immunodeficiency virus, anti-infective agents, biocompatibility, cell culture, cell lines, heparan sulfate, herpes simplex, humans, mechanism of action, mice, models, mucosa, pathogenicity, polymers, proteoglycans, sexually transmitted diseases, vaccination, viral proteins, viruses
Abstract:
The development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like HSV and HIV infections. A suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (HSPGs). AGMA1 is a prevailingly cationic agmatine-containing polyamidoamine polymer previously shown to inhibit HSPGs dependent viruses, including HSV-1, HSV-2, and HPV-16. The aim of this study was to elucidate the mechanism of action of AGMA1 against HSV infection and assess its antiviral efficacy and biocompatibility in preclinical models. The results show AGMA1 to be a non-toxic inhibitor of HSV infectivity in cell cultures and human cervicovaginal histocultures. Moreover, it significantly reduced the burden of infection of HSV-2 genital infection in mice. The investigation of the mechanism of action revealed that AGMA1 reduces cells susceptibility to virus infection by binding to cell surface HSPGs thereby preventing HSV attachment. This study indicates that AGMA1 is a promising candidate for the development of a topical microbicide to prevent sexually transmitted HSV infections.
Agid:
6067809