Mechanistic Studies of Viral Entry: An Overview of Dendrimer-Based Microbicides As Entry Inhibitors Against Both HIV and HSV-2 Overlapped Infections

Med Res Rev. 2017 Jan;37(1):149-179. doi: 10.1002/med.21405. Epub 2016 Aug 12.

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.

Keywords: HIV/HSV-2 entry inhibitors; mechanism of antiviral action; microbicide; polyanionic dendrimer; sexually transmitted infections.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dendrimers / administration & dosage
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • HIV-1 / physiology
  • Herpes Genitalis / drug therapy
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / metabolism
  • Herpesvirus 2, Human / physiology
  • Host-Pathogen Interactions
  • Humans
  • Virus Internalization / drug effects*

Substances

  • Anti-Infective Agents
  • Antiviral Agents
  • Dendrimers