Synthetic Curcumin Analogues Present Antiflavivirus Activity In Vitro with Potential Multiflavivirus Activity from a Thiazolylhydrazone Moiety

Abstract

Arboviral diseases caused by flaviviruses, such as dengue, are a continuing threat and major concern worldwide, with over three billion people estimated to be living with the risk of dengue virus (DENV) infections. There are thus far no antiviral drugs available for treatment, and limited or no vaccines are available. Curcumin and seven synthetic analogues were evaluated for their antiviral activity against dengue virus serotype 2, yellow fever virus and Zika virus, as well as for their cytotoxicity in Vero cells, both by employing MTT assays. Compounds 6 and 7, which present a thiazolylhydrazone moiety, showed moderate activity against all three flaviviruses, with selectivity index (SI) values up to 4.45. In addition, the envelope protein (E) was predicted as the potential target inhibited by both compounds, supported by molecular docking and dynamics simulation analysis. We hope that this data can contribute to the development of new curcumin antiviral analogues in the near future and can help in the search for new promising compounds as potential therapeutic agents to treat flaviviruses infections.

Aminopyrimidine Derivatives as Multiflavivirus Antiviral Compounds Identified from a Consensus Virtual Screening Approach

“…All cell cultures were incubated in a humidified incubator at 37 °C under a 5% CO 2 atmosphere. Viral titration and propagation were performed as previously reported and are described in the Supporting Information. This work is registered in the Sistema Nacional de Gestão do Patrimônio Genético e do Conhecimento Tradicional Associado (SisGen), Brazil, under registration number A7AF7BF.…”

“…Cellular assays with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; Thermo Fischer Scientific, USA) were performed to determine the cytotoxic concentration of 50% (CC 50 ) and the effective concentration of 50% (EC 50 ) as previously described, and are described in the Supporting Information. Compounds were assessed in a serial dilution ranging from 100 to 1.56 μM.…”

“…All cell cultures were incubated in a humidified incubator at 37 °C under a 5% CO 2 atmosphere. Viral titration and propagation were performed as previously reported 84 0 to 300 Å 2 determine the cytotoxic concentration of 50% (CC 50 ) and the effective concentration of 50% (EC 50 ) as previously described, 84 and are described in the Supporting Information. Compounds were assessed in a serial dilution ranging from 100 to 1.56 μM.…”

Evaluating Known Zika Virus NS2B-NS3 Protease Inhibitor Scaffolds via In Silico Screening and Biochemical Assays

“…Viral propagation was conducted according to Serafim et al [ 64 ]. Vero monolayers with 60–80% confluence were washed twice with phosphate-buffered saline (PBS) and infected at a multiplicity of infection (MOI) of 0.01 for ZIKV, approximately one viral particle per 100 cells.…”

“…Following the previous study by Serafim et al [ 64 ], viral titration experiments were performed. Cells seeded in 24-well microplates (8.0 × 10 5 cells per well) were incubated at 37 °C in a 5% CO 2 atmosphere for 24 h. Each well received 100 μL of ZIKV’s serial dilutions in MEM in a 1:10 ratio (10 −1 to 10 −5 ), following adsorption for 1 h. The cells were overlayed with 1.0 mL of 199 media (Cultilab, Brazil) with 2% FBS and 1% carboxymethylcellulose (CMC) (Synth, Diadema, Brazil).…”