title: SARS-like WIV1-CoV poised for human emergence.
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.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Vineet D
authors.initials: VD
authors.lastname: Menachery
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Yount
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Amy C
authors.initials: AC
authors.lastname: Sims
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Kari
authors.initials: K
authors.lastname: Debbink
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079;
authors.forename: Sudhakar S
authors.initials: SS
authors.lastname: Agnihothram
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Gralinski
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Graham
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Trevor
authors.initials: T
authors.lastname: Scobey
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Plante
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Scott R
authors.initials: SR
authors.lastname: Royal
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Jesica
authors.initials: J
authors.lastname: Swanstrom
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Sheahan
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079; Department of Cell Biology and Physiology and Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pickles
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland; Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland; Humabs BioMed SA, Bellinzona, Switzerland;
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: Department of Cell Biology and Physiology and Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland; Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland;
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute-Department of Medicine, Harvard Medical School, Boston MA 02215.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079; rbaric@email.unc.edu.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002478:Cells, Cultured; D002685:Chiroptera / Q000821:virology*; D002522:Chlorocebus aethiops; D021821:Communicable Diseases, Emerging / Q000821:virology*; D003332:Coronaviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D003333:Coronaviridae Infections / Q000517:prevention & control / Q000635:transmission / Q000662:veterinary / Q000821:virology*; D003429:Cross Reactions; D018792:Encephalitis, Viral / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D058507:Host Specificity; D006801:Humans; D008168:Lung / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008958:Models, Molecular; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology; D017354:Point Mutation; D011487:Protein Conformation; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology; D013045:Species Specificity; D064370:Spike Glycoprotein, Coronavirus / Q000235:genetics / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication; D015047:Zoonoses
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D064370:Spike Glycoprotein, Coronavirus; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2
keywords: CoV; SARS; Spike; WIV1; emergence