Antiviral activity of silymarin against chikungunya virus

Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-␤-O-D-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection.

mentioning

confidence: 99%

“…(Fig. 1A) is a glucosylated form of quercetin, a flavonoid compound that has been shown to exhibit antiviral activity against several RNA viruses (18)(19)(20). In order to test the antiviral activity of our compound against ebolavirus, we first calculated the EC 50 and EC 90 values using Vero E6 epithelial cells.…”

mentioning

confidence: 99%

Prophylactic Efficacy of Quercetin 3-β- O - d -Glucoside against Ebola Virus Infection

Qiu

Kroeker

et al. 2016

“…Targeting of several metabolic pathways has revealed anti-CHIKV effects of several licensed drugs (3). Compounds most likely targeting virus entry or host cell-specific components required for virus infection have been described (4)(5)(6)(7)(8). Several nucleosides or nucleotides, acting as pseudosubstrates for CHIKV RNA-dependent RNA polymerase and/or using another, more general mechanism of action, have shown anti-CHIKV activity (9).…”

mentioning

confidence: 99%

Design and Validation of Novel Chikungunya Virus Protease Inhibitors

Das

Puusepp

Varghese

et al. 2016

Self Cite

dChikungunya virus (CHIKV; genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for in silico drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC 50 ) of the most potent inhibitor being ϳ1.5 M. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism. C hikungunya virus (CHIKV; genus Alphavirus, family Togaviridae) is the causative agent of chikungunya fever, a disease that has affected millions in the last decade. It is characterized by high fever, arthralgia, myalgia, headache, and rash. The disease is usually self-limiting; however long-lasting chronic symptoms are observed in nearly 50% of CHIKV-infected patients (1). As there is no approved vaccine or specific licensed antiviral compounds (2), the treatment of CHIKV infection is largely based on relief of symptoms.CHIKV infection can be inhibited by targeting host factors essential for virus infection. Targeting of several metabolic pathways has revealed anti-CHIKV effects of several licensed drugs (3). Compounds most likely targeting virus entry or host cell-specific components required for virus infection have been described (4-8). Several nucleosides or nucleotides, acting as pseudosubstrates for CHIKV RNA-dependent RNA polymerase and/or using another, more general mechanism of action, have shown anti-CHIKV activity (9). In addition, anti-CHIKV effects have been described for several groups of novel synthetic compounds (10-12).Computer-aided design based on molecular docking and molecular dynamics simulations and pharmacophore approach allows identifying potential in silico hits as active inhibitors for different CHIKV replicase proteins. This approach, however, requires the three-dimensional (3D) structure...

“…This inhibition appeared to be more potent than that of the control nucleoside analogs favipiravir and ribavirin, previously described to have anti-CHIKV activity (12,17). A continuous-treatment assay was conducted to evaluate the antiviral activity of the compound against infectious CHIKV replication in Vero cells (18). Briefly, monolayers of Vero cells were treated with different concentrations of the compound, starting from the maximum nontoxic dose.…”

mentioning

confidence: 99%

Characterization of β- d - N ⁴ -Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus

Ehteshami

Tao

Zandi

et al. 2017

Self Cite

Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified ␤-D-N 4 -hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.