Editorial For reprint orders, please contact: Is regulation preventing the development of therapeutics that may prevent future coronavirus pandemics? Timothy P Sheahan*,1 Accepted for publication: 27 November 2017; Published online: 21 February 2018 In the last century, hundreds of new emerging infectious diseases (EIDs) have arisen in human populations most of which originate from wild animals as zoonoses1. The recent surge of zoonotic EIDs in human populations is driven by a constellation of socioeconomic factors including human population growth, eroding public health infrastructures, changes in land use and agriculture and ease of global travel. HIV, Ebola virus, avian infl uenza (H5N1, H7N9, etc.), severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are but a few recent examples of highly virulent, zoonotic viral EIDs that have catastrophically affected global economies and public health2 . Geopolitical fl ux since the 1990s and the potential for weaponizing EIDs provoked the creation of myriad policies aimed at protecting the USA from bioterrorist threats and the accidental release of potential pandemic pathogens from laboratories. Are these policies effective? Are they impacting countermeasure development for current and future EIDs? How are they shaping the direction of individual research programs, the recruitment of new investigators and the stability of impacted fi elds? Below, we discuss our experiences in developing therapeutics against SARS-, MERS- and zoonotic CoV in an ever changing regulatory environment. Gain of function (GOF) research is critical for microbiological research in determining causal relationships betweenamutationanditsphenotype.In2012,twostudiesdescribingGOFmutationsfacilitatingthetransmission of highly pathogenic avian infl uenza in ferrets set off a fi restorm of debate ultimately resulting in a pause of active GOF research and its future funding3 . While infl uenza research was primarily targeted, GOF policies were also extended to studies that could enhance the pathogenicity and/or transmissibility of SARS- and MERS-CoV in mammals, requiring regulatory approval of each experiment by NIH or its equivalent. Since the types of mammals were not specifi ed and the assessment of mutant virus in humans or all the other approximately 5400 mammals was obviously not possible, the GOF policies by nature of their vagueness could never be adequately satisfi ed. During the pause, a risk and benefi t analysis conducted by the National Science Advisory Board for Biosecurity (NSABB) helped guide the creation of Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO) released in January 20174,5. Almost a year later, US Department of Health and Human Services (HHS) lifted the pause and released policy intended to guide funding decisions of new grant applications involving potential pandemic pathogens that have been enhanced for pathogenicity or transmissibility6. While the policies for new grant applications are now clear and in place, the triage process of amendments to currently funded grant applications remains unknown, as oftentimes a new recombinant must be made to address an evolving research question. For CoV researchers, regulatory complexity increased in 2012 when SARS-CoV was designated as a select agent by the HHS and the Centers for Disease Control and Prevention (CDC)7. The Federal Select Agent Program (FSAP) requires those working with pathogens or toxins that pose a severe threat to public health to register and meet certain safety and security standards. Many of the 66 pathogens and toxins accompanying SARS-CoV on the select agent list are infamous including Ebola virus, smallpox and anthrax. As such, the FSAP has many positive FutureVirol. (2018) 13(3), 143146ISSN 1746-079414310.2217/fvl-2017-0143C ?2018 Future Medicine Ltd EditorialSheahan Biennial Review, 77 (2012). https:/www.gpo.gov/fdsys/pkg/FR-2012-10-05/pdf/FR-2012-10-05.pdf 8De Wit E, Van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14(8), 523534 (2016). 9Menachery VD, Yount BL Jr, Sims AC et al. SARS-like WIV1-CoV poised for human emergence. Proc. Natl Acad. Sci. USA 113(11), 30483053 (2016). 10Menachery VD, Yount BL Jr, Debbink K et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21(12), 15081513 (2015). 11Yount B, Denison MR, Weiss SR, Baric RS. Systematic assembly of a full-length infectious cDNA of mouse hepatitis virus strain A59. J. Virol. 76(21), 1106511078 (2002). 12Yount B, Curtis KM, Fritz EA et al. Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. Proc. Natl Acad. Sci. USA 100(22), 1299513000 (2003). 13Donaldson EF, Yount B, Sims AC, Burkett S, Pickles RJ, Baric RS. Systematic as