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Mechanistic Studies of Viral Entry: An Overview of Dendrimer‐Based Microbicides As Entry Inhibitors Against Both HIV and HSV‐2 Overlapped Infections
Author(s) -
SepúlvedaCrespo Daniel,
CeñaDíez Rafael,
Jiménez José Luis,
Ángeles MuñozFernández Ma
Publication year - 2017
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21405
Subject(s) - microbicides for sexually transmitted diseases , viral entry , microbicide , drug , dendrimer , entry inhibitor , virology , human immunodeficiency virus (hiv) , virus , viral envelope , biology , medicine , pharmacology , viral replication , population , biochemistry , environmental health , health services
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.