title: Aminomethylnaphthoquinones and HSV-1: in vitro and in silico evaluations of potential antivirals.
abstract: Herpes simplex viruses (HSV) are leading causes of human infections which result in severe manifestations, especially in neonates, immunocompromised and/or transplanted individuals. Current HSV type-1 (HSV-1) resistance to standard antiviral agents is a therapeutic challenge, especially for treating immunocompromised patients.
  
  
  
  Herein we describe the promising antiviral profile of three 2-aminomethyl-3-hydroxy-1,4-naphthoquinones against HSV-1 using Vero cells.
  
  
  
  The in silico theoretical analysis indicated that the lowest unoccupied molecular orbital (LUMO) and the conformational features of these molecules are important structural features for modulating their biological activity. Our in vitro results showed that these compounds have significant anti-HSV-1 activity comparable to acyclovir, the antiviral currently used clinically. Importantly two of them showed a lower cytotoxicity profile against Vero cells than acyclovir. The inhibitory mechanism analysis using a time-of-addition assay revealed that all compounds inhibit the late phase of lytic replication. Finally, the highest selectivity index of the first tested compound was almost twice as high as that of acyclovir.
  
  
  
  Since resistance is still a problem for treating HSV infections, these compounds present a promising profile toward the development of new strategies for anti-HSV-1 therapy.
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Camilly P
authors.initials: CP
authors.lastname: Pires de Mello
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Nathália S
authors.initials: NS
authors.lastname: Sardoux
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Terra
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.|Laboratório de Inovações em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz (IOC), FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Leonardo C
authors.initials: LC
authors.lastname: Amorim
authors.affiliation: Departamento de Química Inorgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Vargas
authors.affiliation: Departamento de Química Inorgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: da Silva
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Viveca A
authors.initials: VA
authors.lastname: Giongo
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Lucianne F
authors.initials: LF
authors.lastname: Madeira
authors.affiliation: PPBI, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Campus do Valonguinho, Niterói, Brazil.
authors.forename: Izabel Cnp
authors.initials: IC
authors.lastname: Paixão
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D024882:Drug Resistance, Viral; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D016867:Immunocompromised Host; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014709:Vero Cells; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D009285:Naphthoquinones; D000212:Acyclovir