Abstract
Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.
Keywords:
CoV; SARS; Spike; WIV1; emergence.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Angiotensin-Converting Enzyme 2
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Neutralizing / immunology
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Antibodies, Viral / immunology
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Cells, Cultured
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Chiroptera / virology*
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Chlorocebus aethiops
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Communicable Diseases, Emerging / virology*
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Coronaviridae / genetics
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Coronaviridae / immunology
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Coronaviridae / isolation & purification
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Coronaviridae / pathogenicity*
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Coronaviridae / physiology
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Coronaviridae Infections / prevention & control
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Coronaviridae Infections / transmission
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Coronaviridae Infections / veterinary
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Coronaviridae Infections / virology*
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Cross Reactions
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Encephalitis, Viral / virology
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Epithelial Cells / virology
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Host Specificity
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Humans
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Lung / cytology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Models, Molecular
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Peptidyl-Dipeptidase A / genetics
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Peptidyl-Dipeptidase A / physiology
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Point Mutation
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Protein Conformation
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Receptors, Virus / genetics
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Receptors, Virus / physiology
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Recombinant Fusion Proteins / metabolism
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Severe acute respiratory syndrome-related coronavirus / immunology
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Species Specificity
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / physiology
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Vero Cells
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Virus Replication
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Zoonoses
Substances
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Antibodies, Viral
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Receptors, Virus
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Recombinant Fusion Proteins
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Spike Glycoprotein, Coronavirus
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Ace2 protein, mouse
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Angiotensin-Converting Enzyme 2