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140 Publications visible to you, out of a total of 140
Development of a water-dispersible antimicrobial lipid mixture to inhibit African swine fever virus and other enveloped viruses.

Abstract (Expand)

Medium-chain antimicrobial lipids are promising antiviral agents to inhibit membrane-enveloped viruses such as African swine fever virus (ASFV) and influenza A virus (IAV) in livestock applications. … However, current uses are limited to feed pathogen mitigation due to low aqueous solubility and the development of water-dispersible lipid formulations is needed for broader application usage. In this study, we report a water-dispersible antimicrobial lipid mixture of monoglycerides and lactylates that can inhibit ASFV and IAV and exhibits antiviral properties in drinking water and feed matrices. The lipid mixture reduced the viral infectivity of membrane-enveloped ASFV and IAV in aqueous solution in a dose-dependent manner but was inactive against non-enveloped encephalomyocarditis virus (EMCV). Additional ASFV experiments supported that the lipid mixture is virucidal, which was corroborated by polymerase chain reaction (PCR) experiments. Feed mitigation experiments demonstrated that the lipid mixture can also inhibit ASFV infectivity and affected the conformational properties of ASFV p72 structural protein in virus-spiked feed. Mechanistic experiments identified that the lipid mixture rapidly disrupted phospholipid membranes in a micelle-dependent manner, which aligns with the virological data while higher concentrations were needed for virucidal activity than for the onset of membrane disruption. These findings support that water-dispersible antimicrobial lipid mixtures can effectively inhibit ASFV and IAV and have practical advantages for drinking water applications compared to existing medium-chain antimicrobial lipid mitigant options that are formulated as dry powders or oils for in-feed applications.

Authors: Joshua A Jackman, Roza Izmailyan, Rafayela Grigoryan, Tun Naw Sut, Abel Taye, Hovakim Zakaryan, Charles C Elrod

Date Published: 25th Dec 2024

Publication Type: Journal

Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation.

Abstract (Expand)

The COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral … replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening to identify potential inhibitors of Mpro. We screened around 200 million compounds using this integrated methodology, resulting in a shortlist of promising compounds. These were further scrutinized through molecular dynamics simulations, revealing their interaction dynamics with Mpro. Subsequent in vitro assays using the Mpro enzyme identified two compounds exhibiting significant micromolar inhibitory activity. These findings provide valuable scaffolds for the development of advanced therapeutics targeting Mpro. The comprehensive nature of our approach, spanning computational predictions to experimental validations, offers a robust pathway for rapid and efficient identification of potential drug candidates against COVID-19.

Authors: Smbat Gevorgyan, Hamlet Khachatryan, Anastasiya Shavina, Sajjad Gharaghani, Hovakim Zakaryan

Date Published: 21st Dec 2024

Publication Type: Journal

Association of Inflammasome Gene Expression Levels with Pathogenesis of Familial Mediterranean Fever in Armenians

Abstract (Expand)

Mediterranean fever (FMF) is a genetically determined autoinflammatory disease transmitted mostly by an autosomal recessive mechanism and caused by point mutations of the MEFV (Mediterranean FeVer) … gene. The aim of this study was to evaluate the expression of inflammasome genes (p65, Casp1, MEFV, and NLRP3) in patients with FMF compared to controls to understand the changes playing a key role in disease development. We found altered expression levels of the full-length MEFV isoform as well as Casp1 and p65 in FMF patients versus controls. This, once again, highlighted the significance of inflammasome genes in terms of FMF.

Authors: Varduhi Hayrapetyan, Lana Karapetyan, Lilit Ghukasyan, Sofi Atshemyan, Hovsep Ghazaryan, Valentina Vardanyan, Vahan Mukuchyan, Arsen Arakelyan, Roksana Zakharyan

Date Published: 2nd Dec 2024

Publication Type: Journal

Genewise detection of variants in MEFV gene using nanopore sequencing

Abstract (Expand)

Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive … inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for full-length MEFV gene mutation detection to aid in the diagnosis and screening of FMF. We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected. Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMF-associated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary.

Authors: Lilit Ghukasyan, Gisane Khachatryan, Tamara Sirunyan, Arpine Minasyan, Siras Hakobyan, Andranik Chavushyan, Varduhi Hayrapetyan, Hovsep Ghazaryan, Gevorg Martirosyan, Gohar Mkrtchyan, Valentina Vardanyan, Vahan Mukuchyan, Ashot Davidyants, Roksana Zakharyan, Arsen Arakelyan

Date Published: 29th Nov 2024

Publication Type: Journal

Demographic history and genetic variation of the Armenian population

Abstract (Expand)

We introduce a sizable (n = 34) whole-genome dataset on Armenians, a population inhabiting the region in West Asia known as the Armenian highlands. Equipped with this genetic data, we conducted a … whole-genome study of Armenians and deciphered their fine-scale population structure and complex demographic history. We demonstrated that the Armenian populations from western, central, and eastern parts of the highlands are relatively homogeneous. The Sasun, a population in the south that had been argued to have received a major genetic contribution from Assyrians, was instead shown to have derived its slightly divergent genetic profile from a bottleneck that occurred in the recent past. We also investigated the debated question on the genetic origin of Armenians and failed to find any significant support for historical suggestions by Herodotus of their Balkan-related ancestry. We checked the degree of continuity of modern Armenians with ancient inhabitants of the eastern Armenian highlands and detected a genetic input into the region from a source linked to Neolithic Levantine Farmers at some point after the Early Bronze Age. Additionally, we cataloged an abundance of new mutations unique to the population, including a missense mutation predicted to cause familial Mediterranean fever, an autoinflammatory disorder highly prevalent in Armenians. Thus, we highlight the importance of further genetic and medical studies of this population.

Authors: Anahit Hovhannisyan, Pierpaolo Maisano Delser, Anna Hakobyan, Eppie R. Jones, Joshua G. Schraiber, Mariya Antonosyan, Ashot Margaryan, Zhe Xue, Sungwon Jeon, Jong Bhak, Peter Hrechdakian, Hovhannes Sahakyan, Lehti Saag, Zaruhi Khachatryan, Levon Yepiskoposyan, Andrea Manica

Date Published: 25th Nov 2024

Publication Type: Journal

Unveiling Iso- and Aniso-Hydric Disparities in Grapevine-A Reanalysis by Transcriptome Portrayal Machine Learning.

Abstract (Expand)

Mechanisms underlying grapevine responses to water(-deficient) stress (WS) are crucial for viticulture amid escalating climate change challenges. Reanalysis of previous transcriptome data uncovered … disparities among isohydric and anisohydric grapevine cultivars in managing water scarcity. By using a self-organizing map (SOM) transcriptome portrayal, we elucidate specific gene expression trajectories, shedding light on the dynamic interplay of transcriptional programs as stress duration progresses. Functional annotation reveals key pathways involved in drought response, pinpointing potential targets for enhancing drought resilience in grapevine cultivation. Our results indicate distinct gene expression responses, with the isohydric cultivar favoring plant growth and possibly stilbenoid synthesis, while the anisohydric cultivar engages more in stress response and water management mechanisms. Notably, prolonged WS leads to converging stress responses in both cultivars, particularly through the activation of chaperones for stress mitigation. These findings underscore the importance of understanding cultivar-specific WS responses to develop sustainable viticultural strategies in the face of changing climate.

Authors: T. Konecny, A. Asatryan, M. Nikoghosyan, H. Binder

Date Published: 6th Sep 2024

Publication Type: Journal

Pan-cancer analysis of telomere maintenance mechanisms.

Abstract (Expand)

Telomeres, protective caps at chromosome ends, maintain genomic stability and control cell lifespan. Dysregulated telomere maintenance mechanisms (TMMs) are cancer hallmarks, enabling unchecked cell … proliferation. We conducted a pan-cancer evaluation of TMM using RNA sequencing data from The Cancer Genome Atlas for 33 different cancer types and analyzed the activities of telomerase-dependent (TEL) and alternative lengthening of telomeres (ALT) TMM pathways in detail. To further characterize the TMM profiles, we categorized the tumors based on their ALT and TEL TMM pathway activities into five major phenotypes: ALT (high) TEL (low), ALT (low) TEL (low), ALT (middle) TEL (middle), ALT (high) TEL (high), and ALT (low) TEL (high). These phenotypes refer to variations in telomere maintenance strategies, shedding light on the heterogeneous nature of telomere regulation in cancer. Moreover, we investigated the clinical implications of TMM phenotypes by examining their associations with clinical characteristics and patient outcomes. Specific TMM profiles were linked to specific survival patterns, emphasizing the potential of TMM profiling as a prognostic indicator and aiding in personalized cancer treatment strategies. Gene ontology analysis of the TMM phenotypes unveiled enriched biological processes associated with cell cycle regulation (both TEL and ALT), DNA replication (TEL), and chromosome dynamics (ALT) showing that telomere maintenance is tightly intertwined with cellular processes governing proliferation and genomic stability. Overall, our study provides an overview of the complexity of transcriptional regulation of telomere maintenance mechanisms in cancer.

Authors: M. Hakobyan, H. Binder, A. Arakelyan

Date Published: 2nd Jul 2024

Publication Type: Journal

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