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Updated: Mar 30, 2026
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Integrative computational analysis of Marburg virus protein mutations: structural and functional implications of
Emre Aktaş1, Sema Öztürk1, Bilgesu Tarhan1
1Faculty of Art and Science, Molecular Biology and Genetics, Yıldız Technical University, Istanbul, Türkiye.
Abstract:
Marburg virus is a highly virulent filovirus responsible for severe hemorrhagic fever outbreaks with high mortality rates. This study aimed to (1) investigate the structural and functional consequences of mutations in major MARV proteins-particularly Glycoprotein (GP)-and (2) evaluate the antiviral potential of selected plant-derived compounds using computational approaches. Comparative sequence analysis identified recurrent amino acid substitutions in GP, with mutations such as P278L and D364Y predicted to induce structural damage and impact host receptor binding. Molecular dynamics simulations revealed that these mutations disrupted GP stability, altered solvent accessibility, and reduced hydrogen bonding with TYRO3 and MER receptors, potentially facilitating immune evasion and viral adaptability. Disorder prediction analysis further indicated high flexibility around these sites, reinforcing their role as mutational hotspots. To explore potential antiviral strategies, a panel of five plant-derived compounds-Aesculetin, Carvacrol, Cinnamaldehyde, Eugenol, and Geranial-was computationally screened against GP and host cell receptors (AXL, TYRO3, MER). Only Aesculetin demonstrated consistent docking scores below the -5.5 kcal/mol threshold, suggesting limited but measurable binding affinity. Other compounds exhibited weaker interactions and did not meet the minimal binding energy criterion. In contrast, known EBOV/MARV inhibitors (IN-1, IN-2, IN-3) showed significantly stronger and more stable binding profiles across all targets. Protein-ligand interaction analysis revealed that natural compounds formed fewer stabilizing contacts compared to synthetic inhibitors, though Aesculetin engaged in key hydrogen bonds and weak electrostatic/π-cation interactions with GP. Overall, the findings highlight the structural plasticity of MARV GP, the functional relevance of specific mutations, and the potential-albeit limited-of plant-derived compounds as antiviral candidates.
Insights
Marburg virus mutations in its glycoprotein (GP) can alter its structure and function, potentially aiding immune evasion. While some plant compounds show limited antiviral promise, known inhibitors are more effective.
Area of Science:
- Virology and Molecular Biology
- Computational Biochemistry
- Drug Discovery
Background:
- Marburg virus (MARV) is a deadly filovirus causing severe hemorrhagic fever outbreaks.
- Understanding MARV Glycoprotein (GP) mutations is crucial for developing antiviral strategies.
- MARV GP mediates viral entry by interacting with host cell receptors like AXL, TYRO3, and MER.
Purpose of the Study:
- To investigate the structural and functional impact of MARV GP mutations.
- To evaluate the antiviral potential of selected plant-derived compounds against MARV using computational methods.
Main Methods:
- Comparative sequence analysis to identify recurrent MARV GP mutations.
- Molecular dynamics simulations to assess mutation-induced structural changes and receptor interactions.
- Computational screening (docking) of plant compounds (Aesculetin, Carvacrol, Cinnamaldehyde, Eugenol, Geranial) against MARV GP and host receptors.
Main Results:
- Mutations P278L and D364Y in MARV GP were predicted to cause structural damage, reduce receptor binding (TYRO3, MER), and potentially facilitate immune evasion.
- Aesculetin showed minimal binding affinity to MARV GP, while other natural compounds had weaker interactions.
- Known synthetic inhibitors (IN-1, IN-2, IN-3) exhibited significantly stronger binding than the tested plant compounds.
Conclusions:
- MARV GP possesses structural plasticity, with specific mutations impacting its stability and host interactions.
- Plant-derived compounds like Aesculetin have limited potential as MARV antivirals compared to established inhibitors.
- Further research into MARV GP structure-function relationships is warranted for effective antiviral development.
