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101 Publications visible to you, out of a total of 101
Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation

Abstract (Expand)

This paper examines how deep-space conditions in the Artemis program, including radiation, microgravity, and other stressors affect genomic stability in blood-forming cells, with a focus on clonal … hematopoiesis and sex-specific differences in DNA repair and mutation risk. Studies show space conditions promote mutations in hematopoietic stem cells, with sex-specific effects: males are more vulnerable to Y chromosome loss and structural damage, while females may experience increased epigenetic instability despite protective redundancy from the X chromosome; these risks are amplified by combined stressors like radiation, oxidative stress, and circadian disruption. Sex chromosome differences play a key role in radiation-induced mutations and clonal expansion, highlighting the need for personalized, sex-specific medical monitoring and countermeasures rather than a uniform approach for astronauts on long-duration missions.

Authors: Roksana Zakharyan, Ani Stepanyan, Arpine Minasyan, Suren Davitavyan, Gisane Lazaryan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Susmita Sahoo, Shihong Zhang, Venkata Naga Srikanth Garikipati, Mary K. Khlgatian, Arsen Arakelyan, David A. Goukassian

Date Published: 23rd Apr 2026

Publication Type: Journal

Can artificial intelligence transform antiviral drug discovery?

Abstract (Expand)

The development of antiviral therapies is constrained by high costs and extended timelines, often insufficient to address rapidly spreading viral outbreaks. Artificial intelligence (AI) has recently … shown significant progress in identifying and optimizing therapeutic candidates. This review examines the application of AI across four domains in antiviral drug discovery: target identification via host-virus protein-protein interaction prediction and machine-learning analysis of genome-wide CRISPR screens; drug repurposing; de novo molecule design with generative AI; and resistance mutations prediction and phenotypic effects from viral sequence data. We discuss in silico and validated studies, focusing on the limited in vitro and in vivo evidence, and highlight common challenges and key limitations.

Authors: Irina Tirosyan, Yeva Gabrielyan, Vahe Petrosyan, Marco Vignuzzi, Hovakim Zakaryan

Date Published: 22nd Mar 2026

Publication Type: Journal

Multi-target computational pipeline for discovery of pan-influenza neuraminidase inhibitors.

Abstract (Expand)

The continuous evolution of influenza A and B viruses, coupled with the emergence of drug resistance, creates a pressing need for novel antiviral agents with broad-spectrum activity. The viral neuraminidase … enzyme remains a prime target, but its structural variability across different strains complicates the discovery of universal inhibitors. To address this challenge, we developed and implemented a multi-target computational pipeline designed to identify pan-influenza neuraminidase inhibitors. Our strategy involved high-precision molecular docking of a curated library containing 499,721 compounds against three structurally distinct neuraminidase representatives from influenza A (H1N1, H2N2) and influenza B viruses. Hits were prioritized using a cascade of energetic and geometric filters, followed by a rigorous two-tiered validation using extensive molecular dynamics simulations. This validation not only confirmed binding stability on the primary target but also critically assessed whether candidates maintained stable interactions across the other neuraminidase subtypes. This cross-validation approach was essential for eliminating subtype-specific binders, ultimately identifying ten compounds with robust, pan-influenza binding profiles. Notably, the successful identification of a diastereomer of the established drug zanamivir among the top candidates provides strong validation for the pipeline's ability to find biologically relevant scaffolds. Overall, this work demonstrates the integration of multi-target screening with cross-validated molecular dynamics (cross-MD) that overcame target variability and yielded ten promising hits candidates for next-generation anti-influenza therapeutics.

Authors: Smbat Gevorgyan, Marusya Ayvazyan, Levon Kharatyan, Anastasiya Shavina, Narek Abelyan, Hamlet Khachatryan, Hovakim Zakaryan

Date Published: 10th Mar 2026

Publication Type: Journal

Population structure of wild and cultivated grapevines in Armenia

Abstract (Expand)

Background: The South Caucasus region, including Armenia, is recognized as a center of early viticulture, home to the oldest known winery and a rich tradition of winemaking. Armenia's topography … has contributed to the preservation of genetically diverse grapevine populations. Cultivated grapevines (Vitis vinifera ssp. vinifera or V.V. ssp. vinifera) and their wild ancestor (V. vinifera ssp. sylvestris or V.V. ssp. sylvestris) exhibit high genetic diversity, making them valuable resources for understanding domestication, adaptation, and breeding. Despite Armenia’s historical and economic importance, the genomic diversity of its wild and cultivated grapevines remains underexplored. We re-analyzed whole-genome sequencing data of 164 grapevine accessions from Armenia, including cultivated and wild individuals, taken from a previous study on worldwide collected vine accessions to characterize genomic diversity, population structure, and domestication history of this gene pool. Results: Our analysis uncovered genetic patterns partly unique to Armenia. Population structure analysis revealed a clear genetic separation between wild and cultivated groups and three distinct ancestral components within the cultivated gene pool, reflecting a west-to-east geographical gradient in Armenia. This genetic cline correlates with a shift in usage, from table to wine grapes, and a transition in berry skin color from white to black. Additionally, we identified four distinct subgroups within wild populations in Syunik, suggesting notable diversity. Evolutionary history analysis indicates that wild and cultivated lineages began to separate ~18.5k years ago, with divergence intensifying ~4k years ago under human cultivation. Comparative genomic scans for divergent selection identified genomic regions associated with domestication traits, including disease resistance and biosynthesis of anthocyanin and flavanol. Genome-wide association, including k-mer-based approach studies, uncovered candidate markers linked to agronomic traits, such as berry skin color and bunch density. These results provide genomic resources and highlight targets for grapevine improvement and conservation. Conclusions: This whole-genome study on the genetic diversity of wild and cultivated grapevines from Armenia provides a valuable resource for identifying candidate genes and domestication-related regions associated with agronomic traits. The results underscore the importance of conserving local grapevine diversity in Armenia, a historically significant and genetically rich viticultural region.

Authors: Maria Nikoghosyan, Emma Hovhannisyan, Nate Zadirako, Shengchang Duan, Armine Asatryan, Arsen Arakelyan, Kristine Margaryan, Anush Baloyan, Tomas Konecny, Hans Binder

Date Published: 11th Feb 2026

Publication Type: Journal

Development of biobanking infrastructure in Armenia: opportunities and challenges

Abstract (Expand)

Biobanking has become a cornerstone of biomedical research and precision medicine, enabling population studies, biomarker discovery, and translational research. However, while high-income countries … operate mature biobanking systems, middle-income and transitional economies encounter distinct barriers to establishing sustainable and internationally compatible infrastructures. This mini review examines the development of biobanking in Armenia as a representative middle-income case. It highlights key opportunities, such as strong diaspora scientific networks, a growing biotechnology sector, increasing national interest in precision medicine, and Armenia’s strategic geographic position between Europe and Asia. At the same time, significant challenges persist, including limited funding, regulatory and ethical gaps, infrastructure constraints, shortages in specialized technical personnel, and socio-cultural barriers related to sample donation and data sharing. The review outlines strategic approaches adopted in Armenia, including international collaboration, capacity-building initiatives, and alignment with global best practices. Lessons from Armenia’s experience may guide other middle-income and post-Soviet countries in developing effective and resilient biobanking systems.

Authors: Gohar Mkrtchyan, Kristina Avanesyan, Hovsep Ghazaryan, Merry Mazmanian, Marie-Alexandra Alyanakian, Arsene Mekinian, Arsen Arakelyan

Date Published: 13th Jan 2026

Publication Type: Journal

Integrated analysis of the blood metallome and DNA methylation, gene expression, and protein levels of immune-associated genes in residents from mining region

Abstract (Expand)

Environmental exposure to toxic and essential metals can disrupt host immune function through mechanisms involving epigenetic, transcriptional, and post-transcriptional regulation. Although numerous … studies have investigated these regulatory layers separately, integrative analyses across molecular levels in relation to metallome is missing. In this study, we performed a targeted multi-omics analysis of six immune-associated genes (NFKB1, CDKN2A, IGF2, H19, ESR1, and APOA5) and corresponding proteins in healthy residents from a long-term mining region (MRR, n = 46) and a non-mining region (NMR, n = 48). Transcriptome data were generated by mRNA sequencing, while DNA methylation data were obtained using targeted bisulfite sequencing by analyzing previously identified differentially methylated positions. Plasma protein levels were measured by enzyme-linked immunosorbent assay, and plasma metal concentrations were quantified using inductively coupled plasma mass spectrometry. We observed significantly higher plasma levels of NFKB1 and CDKN2A proteins, along with lower ESR1 transcript levels, in residents of the mining region compared to the non-mining region. NFKB1 protein levels were associated with both promoter methylation and residence in mining region, suggesting a regulatory cascade from DNA methylation to protein expression. IGF2 protein levels were higher in males and showed positive associations with age and the cumulative Z-score of essential metal mixture burden. Our results show that long-term residence in mining regions is associated with changes in NFKB1 at both the DNA methylation and protein levels, which may serve as a sensitive biomarker of metal exposure.

Authors: Yeva Bareghamyan, Arpine Minasyan, Suren Davitavyan, Anna Petrackova, Jakub Savara, Romana Nesnadna, Eva Kriegova, Jonathan Schug, Arsen Arakelyan, Ani Stepanyan

Date Published: 4th Jan 2026

Publication Type: Journal

Persistence of Western Diet-Associated Pathway Activity Profiles in Ventricular Tissues

Abstract (Expand)

The consumption of a Western diet (WD), characterized by high levels of fats and sugars, is strongly associated with adverse cardiovascular outcomes. In this case-control study, we evaluated long-term … alterations in signaling pathway activities in the left (LV) and right (RV) ventricular tissues of C57Bl/6J mice that were exposed to WD starting at 300 days of age for 125 days before switching to a normal diet (ND). LV and RV tissues were collected at 530 days and subjected to RNA sequencing. Pathway activity for 40 signaling pathways (comprising 709 pathway branches/sinks) was calculated using the topology-aware Pathway Signal Flow (PSF) algorithm, which assesses signal propagation along a pathway based on gene expression levels of its components and their interactions. We observed significant perturbations in 14 pathway branches specifically in LV tissue of male mice, 105 days after the ND switch. These alterations included the downregulation of cardioprotective VEGF signaling and the upregulation of pro-fibrotic TGF-beta signaling, suggesting lasting cardiovascular risks. Furthermore, strong signaling was detected in the cGMP-PKG and FOXO pathways linked to cardiac failure. Finally, pro- and anti-apoptotic signals were simultaneously upregulated, accompanied by the downregulation of cell cycle inhibitors. Notably, no significant gene expression changes were detected in the left ventricular tissue of females, and no significant differences were observed in right ventricular tissue in either sex. These findings suggest that the effects of a Western diet may persist even after transitioning to a healthier diet. Further studies are needed to elucidate the diet-associated risks and develop strategies to mitigate these long-term effects.

Authors: Tamara Sirunyan, Gisane Lazaryan, Siras Hakobyan, Suren Davitavyan, Ani Stepanyan, Agnieszka Brojakowska, Mary Khlgatian, Malik Bisserier, Shihong Zhang, David Goukassian, Arsen Arakelyan

Date Published: 2nd Jan 2026

Publication Type: Journal

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