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20 Publications visible to you, out of a total of 20
Inhibition of African swine fever virus infection by genkwanin.

Abstract (Expand)

African swine fever virus (ASFV) is the causative agent of an economically important disease of pigs for which no effective vaccines or antiviral drugs are available. Recent outbreaks in EU countries … and China have highlighted the critical role of antiviral research in combating this disease. We have previously shown that apigenin, a naturally occurring plant flavone, possesses significant anti-ASFV activity. However, apigenin is practically insoluble in highly polar solvents and it occurs typically in derivative forms in plants. Here we screened several commercially available apigenin derivatives for their ability to inhibit ASFV Ba71V strain in Vero cells. Among them, genkwanin showed significant inhibition of ASFV, reducing viral titer from 6.5 ± 0.1 to 4.75 ± 0.25 log TCID/ml in a dose-dependent manner (IC<sub>50</sub> = 2.9 μM and SI = 205.2). Genkwanin reduced the levels of ASFV early and late proteins, as well as viral DNA synthesis. Our further experiments indicated that genkwanin is able to inhibit ASFV infection at entry and egress stages. Finally, genkwanin displayed potent antiviral activity against highly virulent ASFV isolate currently circulating in Europe and China, emphasizing its value as candidate for antiviral drug development.

Authors: Astghik Hakobyan, Erik Arabyan, Armen Kotsinyan, Zaven Karalyan, Harutyun Sahakyan, Vahram Arakelov, Karen Nazaryan, Fernando Ferreira, Hovakim Zakaryan

Date Published: 13th Apr 2019

Publication Type: Journal

Genistein inhibits African swine fever virus replication in vitro by disrupting viral DNA synthesis.

Abstract (Expand)

African swine fever virus (ASFV) is the causal agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic consequences in affected countries. Once, neither an … anti-viral drug nor an effective vaccines are available, studies on new anti-ASFV molecules are urgently need. Recently, it has been shown that ASFV type II topoisomerase (ASFV-topo II) is inhibited by several fluoroquinolones (bacterial DNA topoisomerase inhibitors), raising the idea that this viral enzyme can be a potential target for drug development against ASFV. Here, we report that genistein hampers ASFV infection at non-cytotoxic concentrations in Vero cells and porcine macrophages. Interestingly, the antiviral activity of this isoflavone, previously described as a topo II poison in eukaryotes, is maximal when it is added to cells at middle-phase of infection (8 hpi), disrupting viral DNA replication, blocking the transcription of late viral genes as well as the synthesis of late viral proteins, reducing viral progeny. Further, the single cell electrophoresis analysis revealed the presence of fragmented ASFV genomes in cells exposed to genistein, suggesting that this molecule also acts as an ASFV-topo II poison and not as a reversible inhibitor. No antiviral effects were detected when genistein was added before or at entry phase of ASFV infection. Molecular docking studies demonstrated that genistein may interact with four residues of the ATP-binding site of ASFV-topo II (Asn-144, Val-146, Gly-147 and Leu-148), showing more binding affinity (-4.62 kcal/mol) than ATP<sup>4-</sup> (-3.02 kcal/mol), emphasizing the idea that this viral enzyme has an essential role during viral genome replication and can be a good target for drug development against ASFV.

Authors: Erik Arabyan, Astghik Hakobyan, Armen Kotsinyan, Zaven Karalyan, Vahram Arakelov, Grigor Arakelov, Karen Nazaryan, Anna Simonyan, Rouben Aroutiounian, Fernando Ferreira, Hovakim Zakaryan

Date Published: 22nd Jun 2018

Publication Type: Journal

Intracellular African swine fever virus DNA remains unmethylated in infected Vero cells.

Abstract (Expand)

Sequence-specific CpG methylation of eukaryotic promoters is an important epigenetic signal for long-term gene silencing. We have now studied the methylation status of African swine fever virus (ASFV) … DNA at various times after infection of Vero cells in culture.

Authors: Stefanie Weber, Astghik Hakobyan, Hovakim Zakaryan, Walter Doerfler

Date Published: 12th Jan 2018

Publication Type: Journal

Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

Abstract (Expand)

Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting … fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

Editor:

Date Published: 13th Dec 2017

Publication Type: Journal

Evidence of hemolysis in pigs infected with highly virulent African swine fever virus.

Abstract

The research was conducted to understand more profoundly the pathogenetic aspects of the acute form of the African swine fever (ASF).

Authors: Zaven Karalyan, Hovakim Zakaryan, Elina Arakelova, Violeta Aivazyan, Marina Tatoyan, Armen Kotsinyan, Roza Izmailyan, Elena Karalova

Date Published: 14th Dec 2016

Publication Type: Journal

Apigenin inhibits African swine fever virus infection in vitro.

Abstract (Expand)

African swine fever virus (ASFV) is one of the most devastating diseases of domestic pigs for which no effective vaccines are available. Flavonoids, natural products isolated from plants, have been … reported to have significant in vitro and in vivo antiviral activity against different viruses. Here, we tested the antiviral effect of five flavonoids on the replication of ASFV in Vero cells. Our results showed a potent, dose-dependent anti-ASFV effect of apigenin in vitro. Time-of-addition experiments revealed that apigenin was highly effective at the early stages of infection. Apigenin reduced the ASFV yield by more than 99.99 % when it was added at 1 hpi. The antiviral activity of apigenin was further investigated by evaluation of ASFV protein synthesis and viral factories. This flavonoid inhibited ASFV-specific protein synthesis and viral factory formation. ASFV-infected cells continuously treated with apigenin did not display a cytopathic effect. Further studies addressing the use of apigenin in vivo are needed.

Authors: Astghik Hakobyan, Erik Arabyan, Aida Avetisyan, Liana Abroyan, Lina Hakobyan, Hovakim Zakaryan

Date Published: 15th Sep 2016

Publication Type: Journal

African swine fever virus: current state and future perspectives in vaccine and antiviral research.

Abstract (Expand)

African swine fever (ASF) is among the most significant of swine diseases for which no effective vaccines and antivirals are available. The disease, which is endemic in Africa, was introduced to … Trans-Caucasian countries and the Russian Federation in 2007, where it remains prevalent today among domestic pigs and wild boars. Although some measures were implemented, ASF continues to pose a global risk for all countries, and thereby highlighting the importance of vaccine and antiviral research. In this review, an overview of research efforts toward the development of effective vaccines during the past decades is presented. As an alternative to vaccine development, the current state in antiviral research against ASFV is also presented. Finally, future perspectives in vaccine and antiviral research giving emphasis on some strategies that may allow researchers to develop effective countermeasures against ASF are discussed.

Authors: Hovakim Zakaryan, Yolanda Revilla

Date Published: 15th Mar 2016

Publication Type: Journal

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