Oroxylin A shows limited antiviral activity towards dengue virus

Abstract

Objective The mosquito transmitted dengue virus (DENV) the causative agent of dengue fever (DF) remains a significant public health burden in many countries. Thailand, along with many countries in Asia and elsewhere, has a long history of using traditional medicines to combat febrile diseases such as DF. Screening bioactive compounds from traditional medicines reported to have antipyretic or anti-inflammatory activity may lead to the development of potent antivirals. In this study oroxylin A (OA), a flavonoid derivative found in Oroxylum indicum (commonly called the Indian trumpet flower or tree of Damocles), was screened for antiviral activity towards DENV. Results Cytotoxicity analysis in BHK-21 cells showed a 50% cytotoxic concentration (CC50) of 534.17 µM. The compound showed no direct virucidal activity towards DENV, and pre-treatment of cells had no effect on virus production. A deficit was seen in virus production when cells were post-infection treated with oroxylin A. Under conditions of post-infection treatment, the EC50 value was 201.1 µM, giving a selectivity index (SI) value of 2.66. Accumulation of DENV E protein inside the cell was seen under conditions of post-infection treatment, suggesting that oroxylin A may exert some effects at the virus assembly/egress stages of the replication cycle.

Antiviral Activity of an Indole-Type Compound Derived from Natural Products, Identified by Virtual Screening by Interaction on Dengue Virus NS5 Protein

“…On the other hand, it was found that compound M78 induces a reduction in NS5 expression, with a dose-dependent effect ( Figure 4 ), and a predicted selectivity index (SI) of 2.5 µM, indicating that the compound is effective and selective at this concentration. This parameter is accepted to express the efficacy of a compound in inhibiting viral replication, although studies have shown that SI values < 10 have limited antiviral activity, as observed in the case of OA, a methylated flavone from Oroxylum indicum , with an SI of 2.66 against DENV-2 [ 53 ]. Furthermore, by using the replicon system, which allows studying aspects of viral replication due to the lack of structural genes [ 30 ], it is possible to consider that the intervention of M78 is directed towards viral replication and/or the expression of proteins associated with this process [ 54 ], which is also evidenced by the reduction in viral RNA copies ( Figure 5 ), where a 2 −ΔΔCT value less than 1 indicates a reduction in gene expression due to the treatment [ 32 ], estimating that such reduction was 1.7 times greater compared to the viral control.…”

Management of Dengue: An Updated Review

“…In addition, numerous compounds of natural origin, for instance, flavonoids obtained from various plant sources (quercetin, quercitrin, rutin, oroxylin A), curcumin, alpha-mangostin, mangiferin, etc. have been shown to be active against DENV [ 33 – 35 ].…”