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23 Publications visible to you, out of a total of 23

Abstract (Expand)

We have modeled in vitro infection of African swine fever virus (ASFV) in primary unstimulated cells of the porcine bone marrow and have studied the phenotypical changes in the population of porcine lymphoid cells by cytophotometry. Monocytes and large-sized lymphocytes completely vanished in 72 h of infection which is result of high sensitivity of those cells to ASFV. We describe DNA synthesis in monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed the few number of atypical lymphocytes and lymphoblasts after 72 h of cultivation; whereas in viral infected cultures, atypical cells appeared in large quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had altered nucleus, and only a small number of atypical cells had additional nucleus. The cytophotometry of main and additional nuclei showed that DNA content didn't exceed diploid standard which indicates that the additional nuclei were consequence of fragmentation of nuclei in lymphocytes.

Authors: E M Karalova, Kh V Sargsyan, G K Hampikian, H E Voskanyan, L O Abroyan, A S Avetisyan, L A Hakobyan, H H Arzumanyan, H S Zakaryan, Zaven A Karalyan

Date Published: 24th Dec 2010

Publication Type: Journal

Abstract (Expand)

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 > 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2-8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.

Authors: Samvel Sirakanyan, Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Garri Chilingaryan, Harutyun Sahakyan, Arsen Sargsyan, Grigor Arakelov, Karen Nazaryan, Roza Izmailyan, Liana Abroyan, Zaven Karalyan, Elina Arakelova, Elmira Hakobyan, Anush Hovakimyan, Andre Serobian, Marco Neves, João Ferreira, Fernando Ferreira, Hovakim Zakaryan

Date Published: No date defined

Publication Type: Journal

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