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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. 

Background: In the wake of the COVID-19 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real-time. Open-source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real-time remains to be explored. Objective: The objective of this study was to convene experts in public health, infectious diseases, virology, and bioinformatics – many of whom were actively engaged in the COVID-19 response at the time of their participation – to discuss the application of phylodynamic tools to inform pandemic responses. Methods: A series of four virtual focus group discussions were hosted between June 2020 and June 2021, covering the pre- and post-variant and vaccination eras of the COVID-19 crisis. Audio recordings were transcribed verbatim, and an iterative, thematic qualitative framework was used for analysis. Results: Of the 41 individuals invited, 23 total participants (56.1%) agreed to participate. Across the four focus group sessions, 15 (65%) of the participants were female, 17 (74%) were white, and 5 (22%) were black. Participants were described as molecular epidemiologists (ME, n=9), clinician-researchers (n=3), infectious disease experts (ID, n=4), and public health professionals (PH) at the local (n=4), state (n=2), and federal (n=1) levels. Collectively, participants felt that successful uptake of phylodynamic tools relies on the strength of academic-public health partnerships. They called for interoperability standards in sequence data sharing and cited many resource issues that must be addressed, including timeliness and cost, in addition to improving issues related to sampling bias and the translation of phylodynamic findings into public health action. Conclusions: This was the first qualitative study to characterize the perspectives of key experts regarding the utility of phylodynamic tools for the public health response to COVID-19. The focus group participants identified key areas for improvement of existing and future phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology. This information is critical to both policymakers and developers as they consider how to handle existing and emerging SARS-CoV-2 variants during the ongoing crisis.