title: Mechanistic Studies of Viral Entry: An Overview of Dendrimer-Based Microbicides As Entry Inhibitors Against Both HIV and HSV-2 Overlapped Infections.
abstract: This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV/HSV-2. Inhibitors of each entry step have been identified with regard to generations and surface groups, and possible roles for these agents in anti-HIV/HSV-2 therapies have also been discussed. Four potential binding sites for impeding HIV infection (HSPG, DC-SIGN, GSL, and CD4/gp120 inhibitors) and HSV-2 infection (HS, gB, gD, and gH/gL inhibitors) exist according to their mechanisms of action and structures. This review clarifies that inhibition of HIV/HSV-2 entry continues to be a promising target for drug development because nanotechnology can transform the field of HIV/HSV-2 prevention by improving the efficacy of the currently available antiviral treatments.
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors: Daniel
authors: D
authors: Sepúlveda-Crespo
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors: Rafael
authors: R
authors: Ceña-Díez
authors: Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.|Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: José Luis
authors: JL
authors: Jiménez
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors: Ma
authors: M
authors: Ángeles Muñoz-Fernández
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006558:Herpes Genitalis / Q000188:drug therapy / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D000998:Antiviral Agents; D050091:Dendrimers
keywords: HIV/HSV-2 entry inhibitors; mechanism of antiviral action; microbicide; polyanionic dendrimer; sexually transmitted infections