期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 11, 页码 3048-3053出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1517719113
关键词
SARS; CoV; emergence; Spike; WIV1
资金
- National Institute of Allergy and Infectious Disease
- National Institute of Aging of the NIH [U19AI109761, U19AI107810, AI1085524, F32AI102561, K99AG049092]
- National Institute of Diabetes and Digestive and Kidney Disease [NIH DK065988]
- NIH [AI076159, AI079521]
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.
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