title: Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity.
abstract: Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine's potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT) Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT) to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC) with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V). Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.
authors.affiliation: Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Prédio CCS Bloco A, sala 121, 2º andar, CEP: 21941-902, Ilha do Fundão, Rio de Janeiro, Brazil. analu.valadao@gmail.com.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Chaves Valadão
authors.affiliation: Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Prédio CCS Bloco A, sala 121, 2º andar, CEP: 21941-902, Ilha do Fundão, Rio de Janeiro, Brazil. celydion@gmail.com.
authors.forename: Celina Monteiro
authors.initials: CM
authors.lastname: Abreu
authors.affiliation: Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Prédio CCS Bloco A, sala 121, 2º andar, CEP: 21941-902, Ilha do Fundão, Rio de Janeiro, Brazil. juzdias@gmail.com.
authors.forename: Juliana Zanatta
authors.initials: JZ
authors.lastname: Dias
authors.affiliation: Grupo de Bioinformática Estrutural, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, CEP: 91500-970. pablitoarantes@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Arantes
authors.affiliation: Grupo de Bioinformática Estrutural, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, CEP: 91500-970. hverli@cbiot.ufrgs.br.
authors.forename: Hugo
authors.initials: H
authors.lastname: Verli
authors.affiliation: Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Prédio CCS Bloco A, sala 121, 2º andar, CEP: 21941-902, Ilha do Fundão, Rio de Janeiro, Brazil. atanuri@biologia.ufrj.br.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.affiliation: Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Prédio CCS Bloco A, sala 121, 2º andar, CEP: 21941-902, Ilha do Fundão, Rio de Janeiro, Brazil.
authors.forename: Renato Santana
authors.initials: RS
authors.lastname: de Aguiar
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry; D004640:Emetine / Q000008:administration & dosage* / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000470:Alkaloids; D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D004640:Emetine
keywords: HIV-1; PBMC; Reverse Transcriptase; emetine; resistance