Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning Journal Article
| Authors: | Lasso, G.; Grodus, M.; Valencia, E.; DeJesus, V.; Liang, E.; Delwel, I.; Bortz, R. H. 3rd; Lupyan, D.; Ehrlich, H. Y.; Castellanos, A. A.; Gazzo, A.; Wells, H. L.; Wacharapluesadee, S.; Tremeau-Bravard, A.; Seetahal, J. F. R.; Hughes, T.; Lee, J.; Lee, M. H.; Sjodin, A. R.; Geldenhuys, M.; Mortlock, M.; Navarrete-Macias, I.; Gilardi, K.; Willig, M. R.; Nava, A. F. D.; Loh, E. H.; Asrat, M.; Smiley-Evans, T.; Magesa, W. S.; Zikankuba, S.; Wolking, D.; Suzán, G.; Ojeda-Flores, R.; Carrington, C. V. F.; Islam, A.; Epstein, J. H.; Markotter, W.; Johnson, C. K.; Goldstein, T.; Han, B. A.; Mazet, J. A. K.; Jangra, R. K.; Chandran, K.; Anthony, S. J. |
| Article Title: | Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning |
| 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. © 2024 Elsevier Inc. |
| Keywords: | controlled study; protein expression; human cell; nonhuman; binding affinity; heredity; protein degradation; molecular dynamics; prediction; amino acid sequence; nucleotide sequence; species difference; binding site; amino acid; hydrogen bond; virus recombinant; conformational transition; static electricity; virus; virus particle; glycoprotein; protein cleavage; receptor binding; physical chemistry; host; phylogeny; susceptibility; africa; virus entry; geographic distribution; immune evasion; orthology; evolutionary adaptation; virus infectivity; phylogenetic tree; virus glycoprotein; hydrophobicity; binding assay; feature extraction; machine learning; protein-protein interaction; bat; phyllostomidae; species distribution; human; article; random forest; ebola hemorrhagic fever; ebolavirus; vesiculovirus; u2os cell line; cross validation; shapley additive explanation; binding avidity; filovirus; npc1; npc intracellular cholesterol transporter 1; eidolon helvum; flying fox; molossidae; rhinolophidae; vespertilionidae |
| Journal Title: | Cell Host & Microbe |
| Volume: | 33 |
| Issue: | 2 |
| ISSN: | 1931-3128 |
| Publisher: | Cell Press |
| Date Published: | 2025-02-12 |
| Start Page: | 294 |
| End Page: | 313.e11 |
| Language: | English |
| DOI: | 10.1016/j.chom.2024.12.016 |
| PUBMED: | 39818205 |
| PROVIDER: | scopus |
| PMCID: | PMC11825280 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
