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Updated: Jun 2, 2025
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning
Gorka Lasso1, Michael Grodus2, Estefania Valencia1
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Abstract:
Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.
Insights
Bats host filoviruses, but specific species are unknown. This study used binding assays and machine learning to identify bat species most likely to host Ebola virus, aiding future surveillance efforts.
Area of Science:
- Virology
- Genomics
- Ecology
Background:
- Bats are known reservoirs for filoviruses, including Ebola virus.
- The Niemann-Pick C1 (NPC1) protein is crucial for filovirus entry into cells.
- Variations in NPC1 affect viral susceptibility and host specificity.
Purpose of the Study:
- To investigate the binding interactions between filovirus glycoproteins (GPs) and NPC1 orthologs across diverse bat species.
- To identify genetic determinants of filovirus-receptor binding.
- To predict potential bat hosts for filoviruses, particularly Ebola virus.
Main Methods:
- Combinatorial binding assays were performed using seven filovirus GPs and NPC1 from 81 bat species.
- Machine learning models were integrated with binding data to predict binding avidities.
- Bat geographic distribution and historical Ebola outbreak data were combined with binding predictions.
Main Results:
- Filovirus GP-NPC1 binding did not strongly correlate with bat phylogeny.
- Key genetic factors influencing virus-receptor binding were identified.
- A ranking of bat species by their potential as Ebola virus hosts was generated.
Conclusions:
- This study provides a comprehensive analysis of filovirus-receptor interactions in bats.
- A multidisciplinary approach can effectively predict susceptible bat species for filovirus host surveillance.
- The findings aid in identifying high-risk bat populations for filovirus emergence.
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