title: Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C.
abstract: Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4(+) MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC(95) level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. geoffrey.ferir@rega.kuleuven.be
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Férir
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020418:Algal Proteins / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology*; D004357:Drug Synergism; D000077560:Enfuvirtide; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D000077592:Maraviroc; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D037121:Plant Lectins; D000068698:Tenofovir; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D020418:Algal Proteins; D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015700:HIV Envelope Protein gp41; D037102:Lectins; D063065:Organophosphonates; D010446:Peptide Fragments; D037121:Plant Lectins; D014230:Triazoles; D000077560:Enfuvirtide; D000068698:Tenofovir; D000225:Adenine; D000077592:Maraviroc; C499654:griffithsin protein, Griffithsia