Significance

The recent emergence and spread of zoonotic viruses, including Ebola virus and severe acute respiratory syndrome coronavirus 2, demonstrate that animal-sourced viruses are a very real threat to global public health. Virus discovery efforts have detected hundreds of new animal viruses with unknown zoonotic risk. We developed an open-source risk assessment to systematically evaluate novel wildlife-origin viruses in terms of their zoonotic spillover and spread potential. Our tool will help scientists and governments assess and communicate risk, informing national disease prioritization, prevention, and control actions. The resulting watchlist of potential pathogens will identify targets for new virus countermeasure initiatives, which can reduce the economic and health impacts of emerging diseases.

Abstract

The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we are vulnerable to zoonotic viral threats. Strategies are needed to identify and characterize animal viruses that pose the greatest risk of spillover and spread in humans and inform public health interventions. Using expert opinion and scientific evidence, we identified host, viral, and environmental risk factors contributing to zoonotic virus spillover and spread in humans. We then developed a risk ranking framework and interactive web tool, SpillOver, that estimates a risk score for wildlife-origin viruses, creating a comparative risk assessment of viruses with uncharacterized zoonotic spillover potential alongside those already known to be zoonotic. Using data from testing 509,721 samples from 74,635 animals as part of a virus discovery project and public records of virus detections around the world, we ranked the spillover potential of 887 wildlife viruses. Validating the risk assessment, the top 12 were known zoonotic viruses, including SARS-CoV-2. Several newly detected wildlife viruses ranked higher than known zoonotic viruses. Using a scientifically informed process, we capitalized on the recent wealth of virus discovery data to systematically identify and prioritize targets for investigation. The publicly accessible SpillOver platform can be used by policy makers and health scientists to inform research and public health interventions for prevention and rapid control of disease outbreaks. SpillOver is a living, interactive database that can be refined over time to continue to improve the quality and public availability of information on viral threats to human health.

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Data Availability

All datasets along with the R code and R package dependencies needed to fully replicate and evaluate these analyses have been deposited in Open Source Framework (https://osf.io/mb6qn/?view_only=f6326d48d7d941afa7af02714819a1a2) (33).

Acknowledgments

We thank P. Pandit and C. Zambrana-Torellio for analytical support and D. Carroll, A. Clements, and Murray Trostle for their vision and support. This study was made possible by the generous support of the American people through US Agency for International Development (USAID) Emerging Pandemic Threats PREDICT Project Awards GHN-A-00-09-00010-00 and AID-OAA-A-14-00102. USAID had no involvement in the design and content of this manuscript. The contents of this manuscript and associated materials are the responsibility of the authors and do not necessarily reflect the views of USAID or the US Government.

Supporting Information

Appendix (PDF)

References

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Information & Authors

Information

Published in

The cover image for PNAS Vol.118; No.15
Proceedings of the National Academy of Sciences
Vol. 118 | No. 15
April 13, 2021
PubMed: 33822740

Classifications

Data Availability

All datasets along with the R code and R package dependencies needed to fully replicate and evaluate these analyses have been deposited in Open Source Framework (https://osf.io/mb6qn/?view_only=f6326d48d7d941afa7af02714819a1a2) (33).

Submission history

Published online: April 5, 2021
Published in issue: April 13, 2021

Change history

September 16, 2021: The text of this article and SI Appendix have been updated; please see accompanying Correction for details.

Keywords

  1. emerging infectious disease
  2. wildlife
  3. zoonotic virus
  4. disease ecology
  5. public health
  6. mpox

Acknowledgments

We thank P. Pandit and C. Zambrana-Torellio for analytical support and D. Carroll, A. Clements, and Murray Trostle for their vision and support. This study was made possible by the generous support of the American people through US Agency for International Development (USAID) Emerging Pandemic Threats PREDICT Project Awards GHN-A-00-09-00010-00 and AID-OAA-A-14-00102. USAID had no involvement in the design and content of this manuscript. The contents of this manuscript and associated materials are the responsibility of the authors and do not necessarily reflect the views of USAID or the US Government.

Notes

This article is a PNAS Direct Submission. J.D. is a guest editor invited by the Editorial Board.
3The complete lists of Expert Panel and PREDICT Consortium can be found in SI Appendix.
See online for related content such as Commentaries.

Authors

Affiliations

One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
Tracey Goldstein2
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
Christine K. Johnson2
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
Simon Anthony
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
EcoHealth Alliance, New York, NY 1001;
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032;
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032;
Kirsten Gilardi
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
EcoHealth Alliance, New York, NY 1001;
EcoHealth Alliance, New York, NY 1001;
Tammie O’Rourke
Metabiota, Inc., Nanaimo, BC V9S 1G5, Canada;
Global Health, Smithsonian Conservation Biology Institute, Washington, DC 20008;
Wildlife Conservation Society, New York, NY 10460
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;
Jonna A. K. Mazet1 [email protected]
One Health Institute and Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, CA 95616;

Notes

1
To whom correspondence may be addressed. Email: [email protected] or [email protected].
Author contributions: Z.L.G., T.G., C.K.J., S.A., K.G., P.D., K.J.O., T.O., S.M., S.H.O., P.C., and J.A.K.M. designed research; Z.L.G., E.T., G.V., E.P., P.C., and J.A.K.M. performed research; Z.L.G. and J.A.K.M. analyzed data; and Z.L.G., T.G., C.K.J., S.A., K.G., P.D., K.J.O., T.O., S.M., S.H.O., E.T., G.V., and J.A.K.M. wrote the paper.
2
T.G. and C.K.J. contributed equally to this work.

Competing Interests

The authors declare no competing interest.

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