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Project Information

UNDERSTANDING THE RISK OF BAT CORONAVIRUS EMERGENCE

Agency:
NIAID

HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID)
Project Number:
2R01AI110964-06
Contact PI / Project Leader:
DASZAK, PETER
Awardee Organization:
ECOHEALTH ALLIANCE INC

Description

Abstract Text:
Project Summary: Understanding the Risk of Bat Coronavirus Emergence Novel zoonotic, bat-origin CoVs are a significant threat to global health and food security, as the cause of SARS in China in 2002, the ongoing outbreak of MERS, and of a newly emerged Swine Acute Diarrhea Syndrome in China. In a previous R01 we found that bats in southern China harbor an extraordinary diversity of SARSr-CoVs, some of which can use human ACE2 to enter cells, infect humanized mouse models causing SARS-like illness, and evade available therapies or vaccines. We found that people living close to bat habitats are the primary risk groups for spillover, that at one site diverse SARSr-CoVs exist that contain every genetic element of the SARS-CoV genome, and identified serological evidence of human exposure among people living nearby. These findings have led to 18 published peer-reviewed papers, including two papers in Nature, and a review in Cell. Yet salient questions remain on the origin, diversity, capacity to cause illness, and risk of spillover of these viruses. In this R01 renewal we will address these issues through 3 specific aims: Aim 1. Characterize the diversity and distribution of high spillover-risk SARSr-CoVs in bats in southern China. We will use phylogeographic and viral discovery curve analyses to target additional bat sample collection and molecular CoV screening to fill in gaps in our previous sampling and fully characterize natural SARSr-CoV diversity in southern China. We will sequence receptor binding domains (spike proteins) to identify viruses with the highest potential for spillover which we will include in our experimental investigations (Aim 3). Aim 2. Community, and clinic-based syndromic, surveillance to capture SARSr-CoV spillover, routes of exposure and potential public health consequences. We will conduct biological-behavioral surveillance in high-risk populations, with known bat contact, in community and clinical settings to 1) identify risk factors for serological and PCR evidence of bat SARSr-CoVs; & 2) assess possible health effects of SARSr-CoVs infection in people. We will analyze bat-CoV serology against human-wildlife contact and exposure data to quantify risk factors and health impacts of SARSr-CoV spillover. Aim 3. In vitro and in vivo characterization of SARSr-CoV spillover risk, coupled with spatial and phylogenetic analyses to identify the regions and viruses of public health concern. We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential. We will combine these data with bat host distribution, viral diversity and phylogeny, human survey of risk behaviors and illness, and serology to identify SARSr-CoV spillover risk hotspots across southern China. Together these data and analyses will be critical for the future development of public health interventions and enhanced surveillance to prevent the re-emergence of SARS or the emergence of a novel SARSr-CoV.
Project Terms:
Acute; Acute Diarrhea; Address; Amino Acid Sequence; Animals; base; Behavior; Behavioral; Biological; biosecurity; Cells; China; Chiroptera; Clinic; Clinic Visits; Clinical; Communities; community clinic; Coronavirus; Coronavirus Infections; Coupled; Data; Data Analyses; Development; Disease Outbreaks; epidemiologic data; Epithelial Cells; experimental study; exposed human population; exposure route; Exposure to; Family suidae; follow-up; food security; Future; genetic element; Genome; Geographic Distribution; Geography; global health; Habitats; Health; high risk; high risk population; Human; human population study; humanized mouse; In Vitro; in vivo; Individual; Infection; Influenza; Investigation; laboratory experiment; Lead; Maps; Middle East Respiratory Syndrome Coronavirus; Modeling; Molecular; Monoclonal Antibodies; mouse model; Nature; novel; pandemic disease; Paper; Patients; Phylogenetic Analysis; Phylogeny; Prevalence; prevent; Principal Investigator; programs; Proteins; Public Health; public health intervention; Publishing Peer Reviews; Questionnaires; Readiness; Reagent; receptor binding; recombinant virus; respiratory; Risk; Risk Behaviors; Risk Factors; sample collection; Sampling; SARS coronavirus; screening; Serologic tests; Serological; seropositive; Severe Acute Respiratory Syndrome; Site; Surveys; Syndrome; syndromic surveillance; Technology; Testing; Therapeutic Intervention; Therapeutic Monoclonal Antibodies; therapeutic vaccine; Time; trait; Transgenic Organisms; Vaccines; Viral; virology; Virus; Work; Zoonoses

Details

Contact PI / Project Leader Information:
Name:  DASZAK, PETER
Other PI Information:
Not Applicable
Awardee Organization:
Name:  ECOHEALTH ALLIANCE INC
City:  NEW YORK    
Country:  UNITED STATES
Congressional District:
State Code:  NY
District:  10
Other Information:
Fiscal Year: 2019
Award Notice Date: 24-Jul-2019
DUNS Number: 077090066
Project Start Date: 01-Jun-2014
Budget Start Date: 24-Jul-2019
CFDA Code: 855
Project End Date: 30-Jun-2024
Budget End Date: 30-Jun-2020
Agency: ?

Agency: The entity responsible for the administering of a research grant, project, or contract. This may represent a federal department, agency, or sub-agency (institute or center). Details on agencies in Federal RePORTER can be found in the FAQ page.
HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID)
Project Funding Information for 2019:
Year Agency

Agency: The entity responsible for the administering of a research grant, project, or contract. This may represent a federal department, agency, or sub-agency (institute or center). Details on agencies in Federal RePORTER can be found in the FAQ page.

 FY Total Cost
2019 NIAID

HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID)

 		$661,980

Results

i

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ABOUT FEDERAL REPORTER RESULTS

Publications: (17) i

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Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. Journal of virology. 2016 Mar; 90: 3253-6 Yang, Xing-Lou; Hu, Ben; Wang, Bo; Wang, Mei-Niang; Zhang, Qian; Zhang, Wei; Wu, Li-Jun; Ge, Xing-Yi; Zhang, Yun-Zhi; Daszak, Peter; Wang, Lin-Fa; Shi, Zheng-Li Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Bat origin of human coronaviruses. Virology journal. 2015 Dec 22; 12: 221 Hu, Ben; Ge, Xingyi; Wang, Lin-Fa; Shi, Zhengli Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013 Nov 28; 503: 535-8 Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A; Zhu, Guangjian; Epstein, Jonathan H; Mazet, Jonna K; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR. Virologica Sinica. 2016 Feb; 31: 78-80 Wang, Mei-Niang; Zhang, Wei; Gao, Yu-Tao; Hu, Ben; Ge, Xing-Yi; Yang, Xing-Lou; Zhang, Yun-Zhi; Shi, Zheng-Li Pub Med linkPubMed Google Scholar linkGoogle Scholar Google Scholar Cited linkGoogle Scholar Cited
Host and viral traits predict zoonotic spillover from mammals. Nature. 2017 06 29; 546: 646-650 Olival, Kevin J; Hosseini, Parviez R; Zambrana-Torrelio, Carlos; Ross, Noam; Bogich, Tiffany L; Daszak, Peter Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response. Journal of virology. 2016 07 15; 90: 6573-6582 Zeng, Lei-Ping; Gao, Yu-Tao; Ge, Xing-Yi; Zhang, Qian; Peng, Cheng; Yang, Xing-Lou; Tan, Bing; Chen, Jing; Chmura, Aleksei A; Daszak, Peter; Shi, Zheng-Li Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
To Cull, or Not To Cull, Bat is the Question. EcoHealth. 2016 Mar; 13: 6-8 Olival, Kevin J Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Prioritizing the 'Dormant' Flaviviruses. EcoHealth. 2017 03; 14: 1-2 Olival, Kevin J; Willoughby, Anna R Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited
Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature. 2018 04; 556: 255-258 Zhou, Peng; Fan, Hang; Lan, Tian; Yang, Xing-Lou; Shi, Wei-Feng; Zhang, Wei; Zhu, Yan; Zhang, Ya-Wei; Xie, Qing-Mei; Mani, Shailendra; Zheng, Xiao-Shuang; Li, Bei; Li, Jin-Man; Guo, Hua; Pei, Guang-Qian; An, Xiao-Ping; Chen, Jun-Wei; Zhou, Ling; Mai, Kai-Jie; Wu, Zi-Xian; Li, Di; Anderson, Danielle E; Zhang, Li-Biao; Li, Shi-Yue; Mi, Zhi-Qiang; He, Tong-Tong; Cong, Feng; Guo, Peng-Ju; Huang, Ren; Luo, Yun; Liu, Xiang-Ling; Chen, Jing; Huang, Yong; Sun, Qiang; Zhang, Xiang-Li-Lan; Wang, Yuan-Yuan; Xing, Shao-Zhen; Chen, Yan-Shan; Sun, Yuan; Li, Juan; Daszak, Peter; Wang, Lin-Fa; Shi, Zheng-Li; Tong, Yi-Gang; Ma, Jing-Yun Pub Med linkPubMed Google Scholar linkGoogle Scholar Google Scholar Cited linkGoogle Scholar Cited
Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS pathogens. 2017 Nov; 13: e1006698 Hu, Ben; Zeng, Lei-Ping; Yang, Xing-Lou; Ge, Xing-Yi; Zhang, Wei; Li, Bei; Xie, Jia-Zheng; Shen, Xu-Rui; Zhang, Yun-Zhi; Wang, Ning; Luo, Dong-Sheng; Zheng, Xiao-Shuang; Wang, Mei-Niang; Daszak, Peter; Wang, Lin-Fa; Cui, Jie; Shi, Zheng-Li Pub Med linkPubMed Google Scholar linkGoogle Scholar Pub Med Cited linkPubMed Cited Google Scholar Cited linkGoogle Scholar Cited

Patents:

No patents information available for 2R01AI110964-06

Similar Projects

UNDERSTANDING THE RISK OF BAT CORONAVIRUS EMERGENCE

Agency:
NIAID

HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID)
Project Number:
2R01AI110964-06
Contact PI / Project Leader:
DASZAK, PETER
Awardee Organization:
ECOHEALTH ALLIANCE INC
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