Poly(amidoamine)s: Past, present, and perspectives

Ferruti, Paolo

doi:10.1002/pola.26632

Cited by 98 publications

(132 citation statements)

References 227 publications

(364 reference statements)

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“…AGMA1 is water soluble, biodegradable, and biocompatible. Its preparation process is simple, easily scalable, and environmentally friendly, taking place in water or alcohols, at room temperature, and without the need for added catalysts (43). Its activity is not papillomavirus type restricted, since it extends across three HPV species belonging to the Alphapapillomavirus genus of the Papillomaviridae family.…”

Section: Discussionmentioning

confidence: 99%

The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

Cagno

Donalisio

Bugatti

et al. 2015

Antimicrob Agents Chemother

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The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of lowrisk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 g/ml and 0.73 g/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections. Human papillomaviruses (HPVs) are members of the Papillomaviridae family of double-stranded DNA nonenveloped viruses (1). The 8-kb HPV genome is enclosed in a capsid shell comprising major (L1) and minor (L2) structural proteins. Most of the HPVs belonging to the Alphapapillomavirus genus are sexually transmitted and infect the anogenital mucosa. For the great majority of immunocompetent individuals, HPV infections are transient, causing asymptomatic epithelial infections or benign epithelial hyperplasia. Genital warts are the most common lesions, caused mainly by HPV-6 and HPV-11. Small proportions of men and women fail to control viral infections and develop HPV-related malignancies, including carcinoma of the cervix, vulva, vagina, penis, anus, or oropharynx. Several HPV types belonging to HPV species 7 (HPV-18, HPV-39, HPV-45, HPV-59, and HPV-68) or species 9 (HPV-16, HPV-31, HPV-33, HPV-35, HPV-52, HPV-58, and HPV-67) can confer high oncogenic risk. HPV-16 and HPV-18 cause about 70% of all cases of invasive cervical cancer worldwide (followed by HPV-31, HPV-33, and HPV-45) (2).It has been estimated that more than 528,000 new cases of cervical cancer occur every year, and cervical cancer caused 266,000 deaths worldwide in 2012 (3, 4). Eighty-five percent of cervical cancer cases occur in women living in low-socioeconomic settings, primarily due to a lack of access to effective cervical cancer screening programs. No anti-HPV drugs are available to cure HPV lesions; therefore, the current treatments are ablative and directed at the abnormal cells associated with HPV, rather than at the virus itself. The development of new ways to prevent genital infections is essential in order to reduce the burden of HPV diseases. Two prophylactic vaccines, Gardasil and Cervarix, are currently available. The first is designed to protect against oncogenic HPV types 16 and 18 and low-risk HPV types 6 and 11 and therefore is preventive against both cancer and genital warts (5); the ...

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Section: Discussionmentioning

confidence: 99%

The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

Cagno

Donalisio

Bugatti

et al. 2015

Antimicrob Agents Chemother

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“…Poly(amidoamine)s (PAAs) are a family of synthetic and highly biocompatible polymers with a highly versatile structure [22]. They are degradable polymers obtained by Michael-type polyaddition of primary or bis secondary amines to bisacrylamides.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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a b s t r a c tThe 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.

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“…Poly(amidoamine)s (PAAs) are multifunctional tert-amine polymers endowed with high structural versatility, obtained by Michael polyaddition of amines and bis-acrylamides (9). The repeating units of PAAs can be designed to be reminiscent of peptides.…”

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confidence: 99%

Agmatine-Containing Poly(amidoamine)s as a Novel Class of Antiviral Macromolecules: Structural Properties and In Vitro Evaluation of Infectivity Inhibition

Donalisio

Ranucci

Cagno

et al. 2014

Antimicrob Agents Chemother

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c Poly(amidoamine)s (PAAs) are multifunctional tert-amine polymers endowed with high structural versatility. Here we report on the screening of a minilibrary of PAAs against a panel of viruses. The PAA AGMA1 showed antiviral activity against herpes simplex virus, human cytomegalovirus, human papillomavirus 16, and respiratory syncytial virus but not against human rotavirus and vesicular stomatitis virus. The results suggest the contribution of both a polycationic nature and side guanidine groups in imparting antiviral activity.

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Poly(amidoamine)s: Past, present, and perspectives

Cited by 98 publications

References 227 publications

The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

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

Agmatine-Containing Poly(amidoamine)s as a Novel Class of Antiviral Macromolecules: Structural Properties and In Vitro Evaluation of Infectivity Inhibition

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