Filter and export

Publications

What is a Publication?
23 Publications visible to you, out of a total of 23
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

Data-driven discovery of chemical signatures for developing new inhibitors against human influenza viruses.

Abstract (Expand)

This study presents cheminformatics analysis of the antiviral chemical space targeting human influenza A and B viruses. By curating 407,366 small molecules from ChEMBL and PubChem, we evaluated … physicochemical properties, structural motifs, and activity trends across phenotypic and target-based assays. We found that 90.6% of evaluated molecules met Lipinski's Rule of Five, with active compounds exhibiting higher topological polar surface area and hydrogen bond donor groups. Target-specific analyses revealed distinct profiles for neuraminidase (NA) and hemagglutinin (HA) inhibitors, including larger molecular weights and increased rotatable bonds. Structural characterization identified cyclohexene, dihydropyran, and pyrimidine rings as prevalent in highly active molecules, while phthalimide motifs correlated with inactivity. Clustering of phenotypic assay data highlighted four promising and unique antiviral candidates, with unexplored chemical space. We also identified five multi-target scaffolds, including the curcumin-like scaffold, demonstrating dual inhibitory potential against two viral proteins. Molecular docking experiments on molecules within one of these multi-target scaffolds indicated their potential as initial hit candidates. Combined RMSD, PDF and DCCM analyses across molecular dynamics simulations elucidated the binding behaviour of five curcumin-like candidates. Two ligands remained as stable as the reference antivirals, one showed target-specific loss of affinity, and two dissociated rapidly, indicating that the stable pair should be prioritised for subsequent in vitro validation. Overall, the findings of this study can aid computer-aided drug design efforts, contributing to the development of novel antiviral agents against human influenza viruses.

Authors: Levon Kharatyan, Smbat Gevorgyan, Hamlet Khachatryan, Anastasiya Shavina, Astghik Hakobyan, Mher Matevosyan, Hovakim Zakaryan

Date Published: 5th Jun 2025

Publication Type: Journal

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

Antiviral screening of natural, anti-inflammatory compound library against African swine fever virus.

Abstract (Expand)

African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant … elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities.

Authors: Joshua A Jackman, Astghik Hakobyan, Rafayela Grigoryan, Roza Izmailyan, Charles C Elrod, Hovakim Zakaryan

Date Published: 25th Apr 2024

Publication Type: Journal

Glycerol Monolaurate Inhibits Wild-Type African Swine Fever Virus Infection in Porcine Macrophages.

Abstract (Expand)

Naturally abundant antimicrobial lipids, such as fatty acids and monoglycerides, that disrupt membrane-enveloped viruses are promising mitigants to inhibit African swine fever virus (ASFV). Among … mitigant candidates in this class, glycerol monolaurate (GML) has demonstrated particularly high antiviral activity against laboratory-adapted ASFV strains. However, there is an outstanding need to further determine the effects of GML on wild-type ASFV strains, which can have different virulence levels and sensitivities to membrane-disrupting compounds as compared to laboratory-adapted strains. Herein, we investigated the antiviral effects of GML on a highly virulent strain of a wild-type ASFV isolate (Armenia/07) in an in vitro porcine macrophage model. GML treatment caused a concentration-dependent reduction in viral infectivity, and there was a sharp transition between inactive and active GML concentrations. Low GML concentrations had negligible effect on viral infectivity, whereas sufficiently high GML concentrations caused a >99% decrease in viral infectivity. The concentration onset of antiviral activity matched the critical micelle concentration (CMC) value of GML, reinforcing that GML micelles play a critical role in enabling anti-ASFV activity. These findings validate that GML can potently inhibit wild-type ASFV infection of porcine macrophages and support a biophysical explanation to guide antimicrobial lipid performance optimization for pathogen mitigation applications.

Authors: Joshua A Jackman, Erik Arabyan, Hovakim Zakaryan, Charles C Elrod

Date Published: 25th Sep 2023

Publication Type: Journal

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

Powered by
 (v.1.15.0-main)
About ArmLifeBank | Funding and Programmes | Credits | Terms & Conditions | Cookie preferences
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH