β-Carboline derivatives as novel antivirals for herpes simplex virus

International Journal of Antimicrobial Agents
M Micaela GonzalezMaría G Vizoso-Pinto

Abstract

Several commercial and novel synthetic β-carbolines (βCs) were evaluated for their antiviral activity against herpes simplex virus type 1 (HSV-1) using an adapted MTS assay. Of 21 drugs tested, although 11 exerted antiviral activity at non-cytotoxic concentrations, only 3 of them [9-methyl-norharmane (9-Me-nHo), 9-methyl-harmane (9-Me-Ho) and 6-methoxy-harmane (6-MeO-Ho)] completely avoided virus-driven cytopathic effects. Half-maximal effective concentrations (EC50 values) (4.9 ± 0.4, 5.9 ± 0.8 and 19.5 ± 0.3 µM, respectively) and selectivity indexes (88.8, 40.2 and 7.0, respectively) of the latter three βCs against HSV-1 were determined by MTS, flow cytometry and plaque reduction assays. The mode of action of these drugs was also evaluated. According to time-of-addition assays, the selected compounds were not virucidal and did not interfere with attachment or penetration of HSV-1, but interfered with later events of virus infection. Western blot studies showed that early and late protein expression was significantly delayed or even suppressed. Herpes simplex virus type 2 (HSV-2) was also inhibited by the selected substances in a similar manner. Interestingly, 6-MeO-Ho, 9-Me-Ho and 9-Me-nHo restricted HSV-1 ICP0 localisation t...Continue Reading

Citations

Jul 7, 2020·Organic & Biomolecular Chemistry·M Paula DenofrioFranco M Cabrerizo
Sep 12, 2020·Physical Chemistry Chemical Physics : PCCP·Fernando D VillarruelFranco M Cabrerizo
Jan 19, 2021·F1000Research·Bruno Silva AndradeVasco Ariston de Carvalho Azevedo
Jun 8, 2021·RSC Medicinal Chemistry·Atukuri Dorababu
Aug 1, 2021·European Journal of Medicinal Chemistry·Bo Luo, Xinqiang Song
Jul 10, 2019·ACS Applied Materials & Interfaces·Magdalena PachotaMaria Nowakowska
Aug 24, 2021·Frontiers in Microbiology·Maria L AlomarFranco M Cabrerizo
Oct 2, 2020·Mini Reviews in Medicinal Chemistry· FaheemMurugesan Sankaranarayanan

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