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24 Publications visible to you, out of a total of 24
Antiviral activity of brequinar against African swine fever virus infection in vitro.

Abstract (Expand)

African swine fever virus (ASFV) is a double-stranded DNA virus that causes an acute and hemorrhagic disease in domestic swine, resulting in significant economic losses to the global porcine industry. … The lack of vaccines and antiviral drugs highlights the urgent need for antiviral studies against ASFV. Here, we report that brequinar (BQR), which is a specific inhibitor of dihydroorotate dehydrogenase, robustly inhibits ASFV replication in Vero cells, as well as in porcine macrophages. We demonstrate that BQR exerts its antiviral activity in a dose-dependent manner through the depletion of pyrimidine pool. Although BQR does not affect the synthesis of an early viral protein, pI215L, the synthesis of late viral proteins, p17 and p72, is suppressed in the presence of BQR. We also show that BQR is able to induce cellular antiviral response in ASFV-infected macrophages by enhancing the expression of interferon-stimulated genes. Taken together, our study reveals that targeting nucleotide biosynthesis represents a promising strategy for developing antiviral agents against ASFV.

Authors: Rafayela Grigoryan, Erik Arabyan, Roza Izmailyan, Zaven Karalyan, Nuno Jordão, Fernando Ferreira, Hovakim Zakaryan

Date Published: 23rd May 2022

Publication Type: Journal

Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus.

Abstract (Expand)

Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine … industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral mechanisms, which motivates exploration of new antiviral candidates within this class. The objective of this study was to determine whether other flavonoids may significantly inhibit ASFV infection <i>in vitro</i>. We performed a cell-based library screen of 90 flavonoids. Our screening method allowed us to track the development of virus-induced cytopathic effect by MTT in the presence of tested flavonoids. This screening method was shown to be robust for hit identification, with an average Z-factor of 0.683. We identified nine compounds that inhibit ASFV Ba71V strain in Vero cells. Among them, kaempferol was the most potent and exhibited dose-dependent inhibition, which occurred through a virostatic effect. Time-of-addition studies revealed that kaempferol acts on the entry and post-entry stages of the ASFV replication cycle and impairs viral protein and DNA synthesis. It was further identified that kaempferol induces autophagy in ASFV-infected Vero cells, which is related to its antiviral activity and could be partially abrogated by the addition of an autophagy inhibitor. Kaempferol also exhibited dose-dependent inhibition of a highly virulent ASFV Arm/07 isolate in porcine macrophages. Together, these findings support that kaempferol is a promising anti-ASFV agent and has a distinct antiviral mechanism compared to other anti-ASFV flavonoids.

Authors: Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Rafaella Grigoryan, Roza Izmailyan, Aida Avetisyan, Zaven Karalyan, Joshua A Jackman, Fernando Ferreira, Charles C Elrod, Hovakim Zakaryan

Date Published: 21st Oct 2021

Publication Type: Journal

Inhibition of African swine fever virus in liquid and feed by medium-chain fatty acids and glycerol monolaurate.

Abstract (Expand)

The ongoing African swine fever virus (ASFv) epidemic has had a major impact on pig production globally and biosecurity efforts to curb ASFv infectivity and transmission are a high priority. It has … been recently identified that feed and feed ingredients, along with drinking water, can serve as transmission vehicles and might facilitate transboundary spread of ASFv. Thus, it is important to test the antiviral activity of regulatory compatible, antiviral feed additives that might inhibit ASFv infectivity in feed. One promising group of feed additive candidates includes medium-chain fatty acids (MCFA) and monoglyceride derivatives, which are known to disrupt the lipid membrane surrounding certain enveloped viruses and bacteria.

Authors: Joshua A Jackman, Astghik Hakobyan, Hovakim Zakaryan, Charles C Elrod

Date Published: 8th Dec 2020

Publication Type: Journal

Antiviral agents against African swine fever virus.

Abstract (Expand)

African swine fever virus (ASFV) is a significant transboundary virus that continues to spread outside Africa in Europe and most recently to China, Vietnam and Cambodia. Pigs infected with highly … virulent ASFV develop a hemorrhagic fever like illness with high lethality reaching up to 100%. There are no vaccines or antiviral drugs available for the prevention or treatment of ASFV infections. We here review molecules that have been reported to inhibit ASFV replication, either as direct-acting antivirals or host-targeting drugs as well as those that act via a yet unknown mechanism. Prospects for future antiviral research against ASFV are also discussed.

Authors: Erik Arabyan, Armen Kotsynyan, Astghik Hakobyan, Hovakim Zakaryan

Date Published: 17th Jul 2019

Publication Type: Journal

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

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