title: Characterization of antiviral activity of benzamide derivative AH0109 against HIV-1 infection.
abstract: In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 μM in HIV-1-susceptible CD4(+) C8166 T cells. Mechanistic analysis revealed that AH0109 significantly inhibits both HIV-1 reverse transcription and viral cDNA nuclear import. Furthermore, our infection experiments indicated that AH0109 is capable of disrupting the replication of HIV-1 strains that are resistant to the routinely used anti-HIV-1 drugs zidovudine, lamivudine, nevirapine, and raltegravir. Together, these findings provide evidence for a newly identified antiviral molecule that can potentially be developed as an anti-HIV-1 agent.
authors.affiliation: Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Liyu
authors.initials: L
authors.lastname: Chen
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Ao
authors.forename: Kallesh Danappa
authors.initials: KD
authors.lastname: Jayappa
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.forename: Shuiping
authors.initials: S
authors.lastname: Liu
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Yao
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009019:Morphinans / Q000494:pharmacology*; D019829:Nevirapine / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D048348:Reverse Transcription / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: C418216:AH019; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D009019:Morphinans; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine