Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen.
The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection.
Hospital General Universitario Gregorio Marañon, Majadahonda, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Majadahonda, Spain; Spanish HIV HGM Biobank, Majadahonda, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain.
Rafael
R
Ceña-Diez
Hospital General Universitario Gregorio Marañon, Majadahonda, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Majadahonda, Spain; Spanish HIV HGM Biobank, Majadahonda, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain; Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, Spain.
Pilar
P
García-Broncano
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain; Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Francisco Javier
FJ
de la Mata
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain; Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Rafael
R
Gómez
Hospital General Universitario Gregorio Marañon, Majadahonda, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Majadahonda, Spain; Spanish HIV HGM Biobank, Majadahonda, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain.
M Ángeles
MÁ
Muñoz-Fernández
D000287:Administration, Topical; D000476:Alkanesulfonates / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D050091:Dendrimers / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008297:Male; D017646:Organosilicon Compounds / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000378:metabolism; D012661:Semen / Q000187:drug effects / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000476:Alkanesulfonates; D019380:Anti-HIV Agents; C584933:CCR5 protein, human; D015704:CD4 Antigens; D050091:Dendrimers; C000607496:G2-S16 compound; D015699:HIV Envelope Protein gp120; D017646:Organosilicon Compounds; D019713:Receptors, CCR5
G2-S16; HIV-1; SEVI; antiretrovirals; dendrimer; microbicide