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Volume 22, Number 7—July 2016
Online Report

Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Timothy M. Uyeki1Comments to Author , Karl J. Erlandson, George Korch, Michael O’Hara, Michael Wathen, Jean Hu-Primmer, Sally Hojvat, Erik J. Stemmy, and Armen Donabedian1
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (T.M. Uyeki); Office of the Assistant Secretary of Preparedness and Response, Washington, DC, USA (K.J. Erlandson, G. Korch, M. O’Hara, M. Wathen, J. Hu-Primmer, A. Donabedian); Food and Drug Administration, Silver Spring, Maryland, USA (S. Hojvat); National Institutes of Health, Rockville, Maryland, USA (E.J. Stemmy)

Main Article

Table 1

Animal models under development for MERS-CoV, United States*

Source Species Genetic modification Pathology
Perlman Laboratory, University of Iowa, Iowa City, IA
Mouse
 Expressing human DPP4 from adenovirus 5 vector
 Transient and localized expression of human DPP4, mild infection (13)
University of Texas Medical Branch, Galveston, TX
 Mouse
 Knock-in of human DPP4, constitutive promoter
 Expression of human DPP4 throughout the animal, including brain, resulting in relentless weight loss and death within days post infection (14)
Regeneron Pharmaceuticals, Inc., Tarrytown, NY
 Mouse
 Knock-in of human DPP4, natural promoter
 Stable expression of human DPP4 under a natural promotor (e.g., limited to the lung, absent in the brain), with viral replication and lung pathology (15)
NIAID Rocky Mountain Laboratories, Hamilton, MT; NIH/NIAID/Laboratory of Infectious Diseases, Bethesda, MD
 New Zealand white rabbit
 Wild-type
 MERS-CoV spike protein binds wild-type rabbit DPP4 molecule that allows for attachment and infection by MERS-CoV; intranasal infection leads to mild pulmonary disease and increased viral titers (16)
NIAID Rocky Mountain Laboratories
 Rhesus macaque
 Wild-type
 Acute localized to widespread pneumonia with transient clinical disease, similar to mild/moderate human MERS-CoV cases; multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes was observed without evidence of systemic infection (17)
NIAID Rocky Mountain Laboratories
 Marmoset
 Wild-type
 MERS-CoV spike protein binds wild-type marmoset DPP4’ multiple routes of infection used; similar to more severe human MERS-CoV cases; lethality observed (18)
NIAID Rocky Mountain Laboratories Dromedaries Wild-type Infection studies in a small number of dromedaries underway in a large animal BSL-3 facility in the United States (19)

*MERS-CoV, Middle East respiratory syndrome coronavirus; DPP4, dipeptidyl peptidase-4; NIAID, National Institute of Allergy and Infectious Diseases; NIH, National Institutes of Health; BSL-3, Biosafety Level 3.

Main Article

References
  1. World Health Organization. Emergencies preparedness, response: Middle East respiratory syndrome coronavirus (MERS-CoV)—Saudi Arabia. 2016 Apr 27 [cited 2016 Apr 27]. http://www.who.int/csr/don/26-april-2016-mers-saudi-arabia/en/
  2. World Health Organization. Summary of current situation, literature update and risk assessment [updated 2015 July 7; cited 2015 Aug 12]. http://apps.who.int//iris/bitstream/10665/179184/2/WHO_MERS_RA_15.1_eng.pdf
  3. Assiri  A, McGeer  A, Perl  TM, Price  CS, Al Rabeeah  AA, Cummings  DAT, Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369:407–16. DOIPubMedGoogle Scholar
  4. Oboho  IK, Tomczyk  SM, Al-Asmari  AM, Banjar  AA, Al-Mugti  H, Aloraini  MS, 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372:846–54. DOIPubMedGoogle Scholar
  5. Alraddadi  BM, Watson  JT, Almarashi  A, Abedi  GR, Turkistani  A, Sadran  M, Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22:49–55. Epub 2015 Dec 18. DOIPubMedGoogle Scholar
  6. Bin  SY, Heo  JY, Song  MS, Lee  J, Kim  EH, Park  SJ, Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea. Clin Infect Dis. 2016;62:755–60. DOIPubMedGoogle Scholar
  7. Bialek  SR, Allen  D, Alvarado-Ramy  F, Arthur  R, Balajee  A, Bell  D, First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities—May 2014. MMWR Morb Mortal Wkly Rep. 2014;63:431–6 .PubMedGoogle Scholar
  8. Kapoor  M, Pringle  K, Kumar  A, Dearth  S, Liu  L, Lovchik  J, Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States. Clin Infect Dis. 2014;59:1511–8. DOIPubMedGoogle Scholar
  9. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV)—Republic of Korea. 2015 Jul 21 [cited 2016 Jan 5]. http://www.who.int/csr/don/21-july-2015-mers-korea/en/
  10. World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV)—China. 2015 May 30 [cited 2015 Dec 21]. http://www.who.int/csr/don/30-may-2015-mers-china/en/
  11. National Institutes of Health. Middle East respiratory syndrome coronavirus (MERS-CoV) research: current status and future priorities. 2013 Jun 24 [cited 2015 Dec 1]. http://www.niaid.nih.gov/about/organization/dmid/documents/mers-covmeeting.pdf
  12. National Academies of Sciences, Engineering, and Medicine. 2016. Rapid medical countermeasure response to infectious diseases: enabling sustainable capabilities through ongoing public and private-sector partnerships. Workshop summary [cited 2016 Mar 17]. http://www.nap.edu/read/21809/chapter/1
  13. Zhao  J, Li  K, Wohlford-Lenane  C, Agnihothram  SS, Fett  C, Zhao  J, Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A. 2014;111:4970–5. DOIPubMedGoogle Scholar
  14. Agrawal  AS, Garron  T, Tao  X, Peng  B-H, Wakamiya  M, Chan  T-S, Generation of transgenic mouse model of Middle East respiratory syndrome-coronavirus infection and disease. J Virol. 2015 Jan 14;JVI.03427–14. PubMedGoogle Scholar
  15. Pascal  KE, Coleman  CM, Mujica  AO, Kamat  V, Badithe  A, Fairhurst  J, Pre- and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015;213:8738–43 http://dx.doi.org10.1073/pnas.1510830112. DOIPubMedGoogle Scholar
  16. Houser  KV, Gretebeck  L, Ying  T, Wang  Y, Vogel  L, Lamirande  EW, Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)–specific human monoclonal antibody protects rabbits from MERS-CoV infection. J Infect Dis. Epub 2016 Mar 3.
  17. de Wit  E, Rasmussen  AL, Falzarano  D, Bushmaker  T, Feldmann  F, Brining  DL, Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A. 2013;110:16598–603 . DOIPubMedGoogle Scholar
  18. Falzarano  D, de Wit  E, Feldmann  F, Rasmussen  AL, Okumura  A, Peng  X, Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 2014;10:e1004250. DOIPubMedGoogle Scholar
  19. Adney  DR, van Doremalen  N, Brown  VR, Bushmaker  T, Scott  D, de Wit  E, Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg Infect Dis. 2014;20:1999–2005 . DOIPubMedGoogle Scholar
  20. Gretebeck  LM, Subbarao  K. Animal models for SARS and MERS coronaviruses. Curr Opin Virol. 2015;13:123–9.
  21. Baseler  L, de Wit  E, Feldmann  H. A comparative review of animal models of Middle East respiratory syndrome coronavirus infection. Vet Pathol. Epub 2016 Feb 11. PubMedGoogle Scholar
  22. Pascal  KE, Coleman  CM, Mujica  AO, Kamat  V, Badithe  A, Fairhurst  J, Pre- and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015;112:8738–43. DOIPubMedGoogle Scholar
  23. van Doremalen  N, Munster  VJ. Animal models of Middle East respiratory syndrome coronavirus infection. Antiviral Res. 2015;22:28–38. Epub 2015 Jul 16. DOIPubMedGoogle Scholar
  24. Chan  JFW, Yao  Y, Yeung  ML, Deng  W, Bao  L, Jia  L, Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a non-human primate model of common marmoset. J Infect Dis. 2015;212:1904–13. DOIPubMedGoogle Scholar
  25. Johnson  RF, Via  LE, Kumar  MR, Cornish  JP, Yellayi  S, Huzella  L, Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease. Virology. 2015;485:422–30. DOIPubMedGoogle Scholar
  26. Adney  D, Bielefeldt-Ohmann  H, Hartwig  A, Bowen  RA. Infection, replication, and transmission of Middle East respiratory syndrome coronavirus in alpacas. Emerg Infect Dis. 2016 Jun. Epub 2016 Mar 4.
  27. Crameri  G, Durr  PA, Klein  R, Foord  A, Yu  M, Riddell  S. Experimental infection and response to rechallenge of alpacas with Middle East respiratory syndrome coronavirus. Emerg Infect Dis. 2016 Jun. Epub 2016 Mar 7.
  28. Reusken  CBEM, Schilp  C, Raj  VS, De Bruin  E, Kohl  RHG, Farag  EABA, MERS-CoV infection of alpaca in a region where MERS-CoV is endemic [letter]. Emerg Infect Dis. 2016 Jun. Epub 2016 Feb 16.
  29. Song  JY, Cheong  HJ, Choi  MJ, Jeon  JH, Kang  SH, Jeong  EJ, Viral shedding and environmental cleaning in Middle East respiratory syndrome coronavirus infection. Infect Chemother. 2015;47:252–5.
  30. Memish  ZA, Assiri  AM, Al-Tawfiq  JA. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. Int J Infect Dis. 2014;29:307–8. DOIPubMedGoogle Scholar
  31. Office of the Commissioner. MCM Legal, Regulatory and Policy Framework—Emergency Use Authorization; Middle East respiratory syndrome coronavirus (MERS-VoV) EUS information [cited 2015 Oct 1]. http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm182568.htm#MERS
  32. Corman  VM, Müller  MA, Costabel  U, Timm  J, Binger  T, Meyer  B, Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill. 2012;17:20334.PubMedGoogle Scholar
  33. Pas  SD, Patel  P, Reusken  C, Domingo  C, Corman  VM, Drosten  C, First international external quality assessment of molecular diagnostics for Mers-CoV. J Clin Virol. 2015;69:81–5 and. DOIPubMedGoogle Scholar
  34. de Wilde  AH, Jochmans  D, Posthuma  CC, Zevenhoven-Dobbe  JC, van Nieuwkoop  S, Bestebroer  TM, Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014;58:4875–84. Epub 2014 May 19. DOIPubMedGoogle Scholar
  35. Dyall  J, Coleman  CM, Hart  BJ, Venkataraman  T, Holbrook  MR, Kindrachuk  J, Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014;58:4885–93. DOIPubMedGoogle Scholar
  36. Falzarano  D, de Wit  E, Rasmussen  AL, Feldmann  F, Okumura  A, Scott  DP, Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques. Nat Med. 2013;19:1313–7 . DOIPubMedGoogle Scholar
  37. Al-Tawfiq  JA, Momattin  H, Dib  J, Memish  ZA. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis. 2014;20:42–6. DOIPubMedGoogle Scholar
  38. Omrani  AS, Saad  MM, Baig  K, Bahloul  A, Abdul-Matin  M, Alaidaroos  AY, Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:1090–5. DOIPubMedGoogle Scholar
  39. European Medicines Agency. Public summary of opinion on orphan designation. Interferon alfa-n3 for the treatment of Middle East respiratory syndrome. 5 Jan 2016 [cited 2016 Mar 17]. http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2016/01/WC500199406.pdf
  40. Stockman  LJ, Bellamy  R, Garner  P. SARS: Systematic review of treatment effects. PLoS Med. 2006;3:e343. DOIPubMedGoogle Scholar
  41. Warren  TK, Wells  J, Panchal  RG, Stuthman  KS, Garza  NL, Van Tongeren  SA, Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature. 2014;508:402–5. DOIPubMedGoogle Scholar
  42. Adedeji  AO, Singh  K, Kassim  A, Coleman  CM, Elliott  R, Weiss  SR, Evaluation of SSYA10–001 as a replication inhibitor of SARS, MHV and MERS coronaviruses. Antimicrob Agents Chemother. Epub 2014 May 19 [cited 2014 May 22]. http://aac.asm.org/cgi/doi/10.1128/AAC.02994-14
  43. Wycoff  K, Maclean  J, Belle  A, Yu  L, Tran  Y, Roy  C, Anti-infective immunoadhesins from plants. Plant Biotechnol J. 2015;13:1078–93. DOIPubMedGoogle Scholar
  44. Channappanavar  R, Lu  L, Xia  S, Du  L, Meyerholz  DK, Perlman  S, Protective effect of intranasal regimens containing peptidic Middle East respiratory syndrome coronavirus fusion inhibitor against MERS-CoV infection. J Infect Dis. 2015;212:1894–903. DOIGoogle Scholar
  45. Kilianski  A, Mielech  AM, Deng  X, Baker  SC. Assessing activity and inhibition of Middle East respiratory syndrome coronavirus papain-like and 3C-like proteases using luciferase-based biosensors. J Virol. 2013;87:11955–62. DOIPubMedGoogle Scholar
  46. ClinicalTrials.gov. Anti–MERS-COV convalescent plasma therapy [cited 2015 Aug 11]. https://clinicaltrials.gov/ct2/show/NCT02190799
  47. Shultz  D. Cows with human chromosomes enlisted to fight hantavirus. Science. Epub 2014 Nov 25 [cited 2015 Aug 11. http://news.sciencemag.org/biology/2014/11/cows-human-chromosomes-enlisted-fight-hantavirus
  48. Ying  T, Du  L, Ju  TW, Prabakaran  P, Lau  CCY, Lu  L, Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J Virol. 2014;88:7798–806. DOIPubMedGoogle Scholar
  49. Jiang  L, Wang  N, Zuo  T, Shi  X, Poon  KMV, Wu  Y, Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci Transl Med. 2014;6:234ra59. PubMedGoogle Scholar
  50. Tang  XC, Agnihothram  SS, Jiao  Y, Stanhope  J, Graham  RL, Peterson  EC, Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc Natl Acad Sci U S A. 2014;111:E2018–26. DOIPubMedGoogle Scholar
  51. Du  L, Zhao  G, Yang  Y, Qiu  H, Wang  L, Kou  Z, A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in MERS-CoV spike protein. J Virol. 2014;88:7045–53. DOIPubMedGoogle Scholar
  52. Ohnuma  K, Haagmans  BL, Hatano  R, Raj  VS, Mou  H, Iwata  S, Inhibition of Middle East respiratory syndrome coronavirus infection by anti-CD26 monoclonal antibody. J Virol. 2013;87:13892–9. DOIPubMedGoogle Scholar
  53. Corti  D, Zhao  J, Pedotti  M, Simonelli  L, Agnihothram  S, Fett  C, Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. Proc Natl Acad Sci U S A. 2015;112:10473–8. DOIPubMedGoogle Scholar
  54. Zumla  A, Chan  JFW, Azhar  EI, Hui  DSC, Yuen  KY. Coronaviruses—drug discovery and therapeutic options. Nat Rev Drug Discov. Epub 2016 Feb 12.
  55. Johnson  RF, Bagci  U, Keith  L, Tang  X, Mollura  DJ, Zeitlin  L, 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012. Virology. 2016;490:49–58.PubMedGoogle Scholar
  56. Ying  T, Li  H, Lu  L, Dimitrov  DS, Jiang  S. Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes Infect. 2015;17:142–8. DOIPubMedGoogle Scholar
  57. Luke  T, Wu  H, Zhao  J, Channappanavar  R, Coleman  CM, Jiao  JA, Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016;8:326. DOIPubMedGoogle Scholar
  58. Arabi  YM, Arifi  AA, Balkhy  HH, Najm  H, Aldawood  AS, Ghabashi  A, Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389–97 . DOIPubMedGoogle Scholar
  59. Wang  L, Shi  W, Joyce  MG, Modjarrad  K, Zhang  Y, Leung  K, Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun. 2015;6:7712.
  60. Muthumani  K, Falzarano  D, Reuschel  EL, Tingey  C, Flingai  S, Villarreal  DO, A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med. 2015;7:301ra132. PubMedGoogle Scholar
  61. Clinical Trials.gov. Phase I, open label dose ranging safety study of GLS-5300 in healthy volunteers [cited 2016 Mar 17]. https://clinicaltrials.gov/ct2/show/NCT02670187?term=mers-cov&rank=7
  62. Greffex, Inc. MERS [cited 2015 Oct 1]. http://www.greffex.com/vaccines/mers/
  63. Song  F, Fux  R, Provacia  LB, Volz  A, Eickmann  M, Becker  S, Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol. 2013;87:11950–4. DOIPubMedGoogle Scholar
  64. Volz  A, Kupke  A, Song  F, Jany  S, Fux  R, Shams-Eldin  H, Protective efficacy of recombinant modified vaccinia virus Ankara delivering Middle East respiratory syndrome coronavirus spike glycoprotein. J Virol. 2015;89:8651–6. DOIPubMedGoogle Scholar
  65. Wang  L, Shi  W, Joyce  MG, Modjarrad  K, Zhang  Y, Leung  K, Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun. 2015;6:7712.
  66. Almazan  F, DeDiego  ML, Sola  I, Zuniga  S, Nieto-Torres  JL, Marquez-Jurado  S, Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. mBiol 2013;4:e00650-13. PubMedGoogle Scholar
  67. Zhang  N, Channappanavar  R, Ma  C, Wang  L, Tang  J, Garron  T, Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cell Mol Immunol. 2016;13:180–90. DOIPubMedGoogle Scholar
  68. Agnihothram  S, Gopal  R, Yount  BL, Donaldson  EF, Menachery  VD, Graham  RL, Evaluation of serologic and antigenic relationships between Middle Eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses. J Infect Dis. 2014;209:995–1006. DOIPubMedGoogle Scholar
  69. Tseng  CT, Sbrana  E, Iwata-Yoshikawa  N, Newman  PC, Garron  T, Atmar  RL, Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS ONE. 2012;7:e35421. DOIPubMedGoogle Scholar
  70. Dodge  J. Camels emit dangerous MERS virus, CSU confirms. November 2014 [cited 2015 Oct 2]. http://source.colostate.edu/camels-emit-mers/
  71. Kupferschmidt  K. MERS surges again, but pandemic jitters ease. Science. 2015;347:1296–7. DOIPubMedGoogle Scholar
  72. Kim  E, Okada  K, Kenniston  T, Raj  VS, AlHajri  MM, Farag  EA, Immunogenicity of an adenoviral-based Middle East respiratory syndrome coronavirus vaccine in BALB/c mice. Vaccine. 2014;32:5975–82. DOIPubMedGoogle Scholar
  73. Khalafalla  AI, Lu  X, Al-Mubarak  AIA, Dalab  AHS, Al-Busadah  KAS, Erdman  DD. MERS-CoV in upper respiratory tract and lungs of dromedary camels, Saudi Arabia, 2013–2014. Emerg Infect Dis. 2015;21:1153–8. DOIPubMedGoogle Scholar
  74. Hemida  MG, Chu  DKW, Poon  LLM, Perera  RAPM, Alhammadi  MA, Ng  H, MERS coronavirus in dromedary camel herd, Saudi Arabia. Emerg Infect Dis. 2014;20:1231–4. DOIPubMedGoogle Scholar
  75. Farag  EA, Reusken  CB, Haagmans  BL, Mohran  KA, Raj  V, Pas  SD, High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014. Infect Ecol Epidemiol. 2015;5:28305. PubMedGoogle Scholar
  76. Haagmans  BL, van den Brand  JMA, Raj  VS, Volz  A, Wohlsein  P, Smits  SL, An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science. 2016;351:77–81. DOIPubMedGoogle Scholar
  77. Food and Drug Administration. Guidances (Drugs) [cited 2015 Aug 11]. http://www.fda.gov/Drugs/GuidancecomplianceRegulatoryInformation/Guidances/default.htm
  78. Saad  M, Omrani  AS, Baig  K, Bahloul  A, Elzein  F, Matin  MA, Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301–6. DOIPubMedGoogle Scholar
  79. Assiri  A, Al-Tawfiq  JA, Al-Rabeeah  AA, Al-Rabiah  FA, Al-Hajjar  S, Al-Barrak  A, Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13:752–61. DOIPubMedGoogle Scholar
  80. Ng  DL, Al Hosani  F, Keating  MK, Gerber  SI, Jones  TL, Metcalfe  MG, Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in United Arab Emirates, April 2014. Am J Pathol. 2016;186:652–8. Epub 2016 Feb 5. DOIPubMedGoogle Scholar
  81. Chu  H, Zhou  J, Wong  BHY, Li  C, Chan  JFW, Cheng  ZS, Middle East respiratory syndrome coronavirus efficiently infects human primary T lymphocytes and activates the extrinsic and intrinsic apoptosis pathways. J Infect Dis. 2016;904–14. http:DOIGoogle Scholar
  82. International Severe Acute Respiratory and Emerging Infection Consortium. Severe acute respiratory infection data tools [cited 2015 Aug 11]. https://isaric.tghn.org/protocols/severe-acute-respiratory-infection-data-tools/
  83. Dunning  JW, Merson  L, Rohde  GGU, Gao  Z, Semple  MG, Tran  D, Open source clinical science for emerging infections. Lancet Infect Dis. 2014;14:8–9 and.PubMedGoogle Scholar
  84. World Health Organization. Clinical management of severe acute respiratory infection when Middle East respiratory syndrome coronavirus (MERS-CoV) infection is suspected. Interim guidance. Updated 2 July 2015 [cited 2015 Aug 11]. http://apps.who.int/iris/bitstream/10665/178529/1/WHO_MERS_Clinical_15.1_eng.pdf
  85. Meyer  B, Juhasz  J, Barua  R, Das Gupta  A, Hakimuddin  F, Corman  VM, Time course of MERS-CoV infection and immunity in dromedary camels. Emerg Infect Dis. 2016 Dec [cited 2016 June 3]. http://dx.doi.org/10.3201/eid2212.160382

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1These authors contributed equally to this article.

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