Antiviral therapy is crucial for the circumvention of
viral epidemics. The
unavailability of a specific antiviral drug against the chikungunya
virus (CHIKV) disease has created an alarming situation to identify
or develop potent chemical molecules for remedial management of CHIKV.
In the present investigation, in silico
studies of dihydrorugosaflavonoid derivatives (5a–f) with non-structural protein-3 (nsP3) were carried out.
nsP3 replication protein has recently been considered as a possible
antiviral target in which crucial inhibitors fit into the adenosine-binding
pocket of the macrodomain. The 4′-halogenated dihydrorugosaflavonoids
displayed intrinsic binding with the nsp3 macrodomain (PDB ID: 3GPO)
of CHIKV. Compounds 5c and 5d showed docking
scores of −7.54 and −6.86 kcal mol–1, respectively. Various in vitro assays were performed to confirm
their (5a–f) antiviral potential
against CHIKV. The non-cytotoxic dose was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay and was found to be <100 μM. The compounds 5c and 5d showed their inhibitory potential for
CHIKV, which was determined
through cytopathic effect assay and plaque reduction assay, which
show inhibition up to 95 and 92% for 70 μM concentration of
the compounds, respectively. The quantitative real-time polymerase
chain reaction assay result confirmed the ability of 5c and 5d to reduce the viral RNA level at 70 μM
concentration
of compounds to nearly 95 and 93% concentration, respectively, in
cells with CHIKV infection. Further, the CHIKV-inhibitory capacity
of these compounds was corroborated by execution of immunofluorescence
assay. The executed work will be meaningful for the future research
of studied dihydrorugosaflavonoids against prime antiviral entrants,
leading to remedial management
to preclude CHIKV infection.
In our earlier studies, an ethanol extract of Curcuma amada Roxb. rhizome was reported for anti-inflammatory activity. This ethanol extract was successively partitioned with hexane and ethyl acetate. Each fractionated extract was screened for anti-inflammatory activity, and the most active fraction was purified by column chromatography. This resulted in isolation of the active fraction F, which was characterized by spectral methods. Fraction F was studied for its effect on general behavioral studies in albino mice. Based on these observations, pharmacological investigations were carried out by adopting the following methods in albino mice: effect on exploratory activity, barbiturate sleeping time, acetic acid-induced writhing, and tail-flick test. This fraction showed reduction in exploratory activity and potentiation of barbiturate sleeping time, indicating CNS depressant activity. Further, it also showed reduction in acetic acid-induced writhings, tail-flick response, and carrageenan-induced inflammation, indicating potential antinociceptive and antiphlogistic activity, respectively.
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