EcoHealth Alliance Receives NIH Renewal Grant for Collaborative Research to Understand the Risk of Bat Coronavirus Spillover Emergence
May 8 2023 – Zoonotic coronaviruses (CoVs) represent a significant threat to global health, as demonstrated by the emergence of SARS-CoV, MERS-CoV and SARS-CoV-2. Bats were identified as the wildlife reservoirs of SARS-CoV by EcoHealth Alliance, and since then, we have published hundreds of novel SARS-related CoV (SARSr-CoV) sequences from wildlife in China and across Southeast Asia. Our work has demonstrated that bats in this region harbor an extraordinary diversity of SARSr-CoVs, some of which can use human ACE2 for cell entry, and can infect humanized mouse models to cause SARS-like illness and evade available therapies or vaccines. Our surveillance studies found serological evidence of prior bat-SARSr-CoV infections in people in rural China before the COVID-19 outbreak. We used these data and other published studies to estimate that more than 66,000 people are infected by bat-SARSr-CoVs each year, with significant potential for future public health impacts. These findings have led to 30 published peer-reviewed scientific reports, and substantial advances in our understanding of how coronaviruses emerge. Yet salient questions remain on the origin, diversity, capacity to cause illness, and risk of spillover of these viruses to people.
To address these questions, EcoHealth Alliance recently received a renewal grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health. The objectives of the project are to (1) characterize and analyze more than 300 new whole genomes and large genome segments of SARSr-CoVs from our archived samples to determine the processes underlying coronavirus recombination and identify viral strains with a high predicted risk of spillover; (2) analyze archived samples from community- and clinic-based syndromic surveillance of people to identify evidence of spillover, assess behavioral risk factors, and pinpoint evidence of illness; and (3) conduct in vitro viral characterization and in silico analysis of epidemiological data to identify hotspots of further CoV spillover risk.
This grant reflects a reversal of the previous termination and suspension of an R01 awarded in 2019, but halted in April 2020 due to concerns about continuing collaborative laboratory research with the Wuhan Institute of Virology. The specific aims have been revised in consultation with NIAID and NIH staff and respond to any ongoing concerns by removing all on-the-ground work in China and all recombinant virus culture or infection experiments. We have also agreed to all additional oversight mechanisms applied by NIH. The renewed work will involve collaboration only between EcoHealth Alliance and the Duke-National University of Singapore Medical School, with the following specific aims: (1) identifying high-spillover risk bat SARSr-CoV sequences in southern China and assessing drivers of recombination; (2) conducting community- and clinic-based surveillance of archived pre-COVID-19 human samples to identify SARSr-CoV spillover events, routes of exposure, and potential public health consequences; and (3) characterizing SARSr-CoV binding, ability to evade therapeutics/vaccines, and identifying spillover hotspots.
This project will provide a proof-of-concept by demonstrating a model platform to integrate analysis of virological, molecular, and ecological factors contributing to CoV emergence while informing high-impact strategies to intervene and prevent future pandemics. The work will also provide critical reagents, identify targets for therapeutic interventions and vaccine development, and viral genome sequences for future SARSr-CoV pandemic and public health preparedness.
Because of the intense public interest in coronavirus research, EcoHealth Alliance has taken the unusual step of releasing full details of the modifications to the previously halted grant “Understanding the risk of bat coronavirus emergence” (NIAID Award #R01AI110964) that this project represents. Normally, grant proposals are sent to federal agencies for review and, if the proposal is funded, they are not usually made public because they contain plans of work that will happen over the subsequent five years, with details of staffing and planned collaborations that public disclosure might jeopardize. However, in an effort to help provide an accurate understanding of the research, and with the aim of being transparent about the study’s goals, EcoHealth Alliance has therefore published the Notice of Award to EcoHealth Alliance from NIH, including all administrative oversight conditions, the ‘Specific Aims’, ‘Project Summary/Abstract’ and ‘Public Health Relevance’ sections (the only sections that have been modified from the original funded proposal, as well as a web summary of the aims of the work, and of its importance for global public health.
Our detailed description of this project lays out why it is important to study these questions of disease spillover risk in emerging infectious disease hotspots to be better prepared to deal with the next pandemic. It clarifies that the work does not involve recombinant virus technology, dual use research of concern, nor experiments intended to enhance the virulence or transmissibility of human pathogens (so-called “gain of function” research). The research in this study is focused on bat coronaviruses, to understand how, when, and under what conditions they are likely to spillover from bats to other mammals, including humans.
The results of this work will be made public rapidly through scientific peer-reviewed papers, preprints, and presentations. We look forward to conducting this critical work to contribute to developing the knowledge that will enable the global community to prevent the next pandemic – a central element of EcoHealth Alliance’s core mission.
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The project referred to in this statement is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI110964. The content is solely the responsibility of the EcoHealth Alliance and does not necessarily represent the official views of the National Institutes of Health.