initiated after the University of North Carolina Institutional Biosafety Committee approved the experimental protocol: Project Title: Generating infectious clones of Bat SARS-like CoVs; Lab Safety Plan ID: 20145741; Schedule G ID: 12279. These studies were initiated prior to the U.S. Government Deliberative Process Research Funding Pause on Selected Gain of Function Research Involving Influenza, MERS, and SARS Viruses (http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf), and the current manuscript has been reviewed by the funding agency, the National Institutes of Health (NIH). Continuation of these studies have been requested and approved by NIH. Menachery et al. Page 8 Nat Med. Author manuscript; available in PMC 2016 June 01. Author Manuscript Author Manuscript Author Manuscript Author Manuscript SARS-CoV is a select agent All work for these studies was performed with approved standard operating procedures (SOPs) and safety conditions for SARS-CoV, MERs-CoV and other related CoVs. Our institutional CoV BSL3 facilities have been designed to conform to the safety requirements recommended in Biosafety in Microbiological and Biomedical Laboratories (BMBL), the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control (CDC) and the NIH. Laboratory safety plans have been submitted, and the facility has been approved for use by the UNC Department of Environmental Health and Safety (EHS) and the CDC. Electronic card access is required for entry into the facility. All workers have been trained by EHS to safely use powered air purifying respirators (PAPRs), and appropriate work habits in a BSL3 facility and active medical surveillance plans are in place. Our CoV BSL3 facilities contain redundant fans, emergency power to fans, and biological safety cabinets and freezers and can accommodate SealSafe mouse racks. Materials classified as BSL3 agents will consist of SARS-CoV, bat CoV precursor strains, MERS-CoV, and mutants derived from these pathogens. Within the BSL3 facilities, experimentation with infectious virus will be performed in a certified Class II Biosafety Cabinet (BSC). All staff wear scrubs, PAPRs, tyvek suits and aprons, and shoe covers, and hands are double-gloved. BSL3 users are subject to a medical surveillance plan monitored by the University Employee Occupational Health Clinic (UEOHC), which includes a yearly physical, annual influenza vaccination, and mandatory reporting of any symptoms associated with CoV infection during periods when working in the BSL3. All BSL3 users are trained in exposure management and reporting protocols, are prepared to self-quarantine, and have been trained for safe delivery to a local infectious disease management department in an emergency situation. All potential exposure events are reported and investigated by EHS and UEOHC, with reports filed to both the CDC and the NIH. Supplementary Material Refer to Web version on PubMed Central for supplementary material. Acknowledgments Research in this manuscript was supported by grants from the National Institute of Allergy & Infectious Disease and the National Institute of Aging of the National Institutes of Health (NIH) under awards U19AI109761 (RSB), U19AI107810 (RSB), AI1085524 (WM), F32AI102561 (VDM), K99AG049092 (VDM); and National Natural Science Foundation of China Award 81290341 (ZLS) and 31470260 (XYG). Human airway epithelial cultures were supported by the National Institute of Diabetes and Digestive and Kidney Disease under award NIH DK065988 (SHR). The authors also recognize MT Ferris, Dept. of Genetics, University of North Carolina for review of statistical approaches and CT Tseng, Dept. of Microbiology and Immunology, University of Texas Medical Branch for provision of Calu3 cells. Experiments with the full length and chimeric SHC014 recombinant viruses were initiated and performed prior to the gain of function research funding pause and have since been reviewed and approved for continued study by NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. References 1. Becker MM, et al. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105:19944–19949.10.1073/pnas.0808116105 [PubMed: 19036930] Menachery et al. Page 9 Nat Med. Author manuscript; available in PMC 2016 June 01. 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