SARS and MERS: recent insights into emerging coronaviruses

Key Points

  • Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that can cause severe respiratory disease in humans. Although disease progression is fairly similar for SARS and MERS, the case fatality rate of MERS is much higher than that of SARS.

  • Comorbidities have an important role in SARS and MERS. Several risk factors are associated with progression to acute respiratory distress syndrome (ARDS) in SARS and MERS cases, especially advanced age and male sex. For MERS, additional risk factors that are associated with severe disease include chronic conditions such as diabetes mellitus, hypertension, cancer, renal and lung disease, and co-infections.

  • Although the ancestors of SARS-CoV and MERS-CoV probably circulate in bats, zoonotic transmission of SARS-CoV required an incidental amplifying host. Dromedary camels are the MERS-CoV reservoir from which zoonotic transmission occurs; serological evidence indicates that MERS-CoV-like viruses have been circulating in dromedary camels for at least three decades.

  • Human-to-human transmission of SARS-CoV and MERS-CoV occurs mainly in health care settings. Patients do not shed large amounts of virus until well after the onset of symptoms, when patients are most probably already seeking medical care. Analysis of hospital surfaces after the treatment of patients with MERS showed the ubiquitous presence of infectious virus.

  • Our understanding of the pathogenesis of SARS-CoV and MERS-CoV is still incomplete, but the combination of viral replication in the lower respiratory tract and an aberrant immune response is thought to have a crucial role in the severity of both syndromes.

  • The severity of the diseases that are caused by emerging coronaviruses highlights the need to develop effective therapeutic measures against these viruses. Although several treatments for SARS and MERS (based on inhibition of viral replication with drugs or neutralizing antibodies, or on dampening the host response) have been identified in animal models and in vitro studies, efficacy data from human clinical trials are urgently required.


The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: SARS-CoV and MERS-CoV structure and replication.
Figure 2: The emergence of SARS-CoV and MERS-CoV.
Figure 3: Evasion of the innate immune response by SARS-CoV and MERS-CoV.


  1. 1

    Zhong, N. S. et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet 362, 1353–1358 (2003).

  2. 2

    Lee, N. et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 348, 1986–1994 (2003).

  3. 3

    Guan, Y. et al. Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome. Lancet 363, 99–104 (2004).

  4. 4

    Drosten, C. et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348, 1967–1976 (2003).

  5. 5

    Ksiazek, T. G. et al. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 348, 1953–1966 (2003).

  6. 6

    Peiris, J. S. et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361, 1319–1325 (2003).

  7. 7

    WHO. Summary of probably SARS cases with onset of illness from 1 November 2002 to 31 July 2003. WHO, (2004).

  8. 8

    Wang, M. et al. SARS-CoV infection in a restaurant from palm civet. Emerg. Infect. Dis. 11, 1860–1865 (2005).

  9. 9

    Ge, X. Y. et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 503, 535–538 (2013). The isolation of a bat SARS-CoV-like virus that uses the human ACE2 as a receptor without prior adaptation, which suggests the potential for emergence without prior adaptation.

  10. 10

    Menachery, V. D. et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med. 21, 1508–1513 (2015). An assessment of the zoonotic potential of SARS-CoV-like viruses circulating in bats.

  11. 11

    Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D. & Fouchier, R. A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814–1820 (2012). The first identification of MERS-CoV as the cause of severe lower respiratory disease in humans.

  12. 12

    Hijawi, B. et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East. Mediterr. Health J. 19 (Suppl. 1), S12–S18 (2013).

  13. 13

    Wise, J. Patient with new strain of coronavirus is treated in intensive care at London hospital. BMJ 345, e6455 (2012).

  14. 14

    Korea Centers for Disease Control and Prevention. Middle East respiratory syndrome coronavirus outbreak in the Republic of Korea, 2015. Osong Public Health Res. Perspect. 6, 269–278 (2015).

  15. 15

    WHO. Coronavirus infections: disease outbreak news. WHO, (2016).

  16. 16

    Pasternak, A. O., Spaan, W. J. & Snijder, E. J. Nidovirus transcription: how to make sense...? J. Gen. Virol. 87, 1403–1421 (2006).

  17. 17

    Perlman, S. & Netland, J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7, 439–450 (2009).

  18. 18

    Fehr, A. R. & Perlman, S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 1282, 1–23 (2015).

  19. 19

    Knoops, K. et al. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 6, e226 (2008).

  20. 20

    Snijder, E. J. et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J. Mol. Biol. 331, 991–1004 (2003).

  21. 21

    Eckerle, L. D. et al. Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLoS Pathog. 6, e1000896 (2010). The finding that nsp14 has a crucial role in the proofreading ability of SARS-CoV.

  22. 22

    Sevajol, M., Subissi, L., Decroly, E., Canard, B. & Imbert, I. Insights into RNA synthesis, capping, and proofreading mechanisms of SARS-coronavirus. Virus Res. 194, 90–99 (2014).

  23. 23

    Raj, V. S. et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495, 251–254 (2013). The demonstration that DPP4 is the receptor for MERS-CoV.

  24. 24

    Masters, P. S. & Perlman, S. in Fields Virology (eds Knipe, D. M. & Howley, P. M.) 825–858 (Wolters Kluwer, 2013).

  25. 25

    Guan, Y. et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302, 276–278 (2003).

  26. 26

    Wang, L. F. et al. Review of bats and SARS. Emerg. Infect. Dis. 12, 1834–1840 (2006).

  27. 27

    Drexler, J. F., Corman, V. M. & Drosten, C. Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS. Antiviral Res. 101, 45–56 (2014).

  28. 28

    Reusken, C. B. et al. Middle East respiratory syndrome coronavirus neutralizing serum antibodies in dromedary camels: a comparative serological study. Lancet Infect. Dis. 13, 859–866 (2013). The first of several papers to provide serological evidence for the circulation of MERS-CoV among dromedary camels; this finding eventually led to the identification of dromedary camels as the main reservoir for MERS-CoV.

  29. 29

    Haagmans, B. L. et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 14, 140–145 (2014).

  30. 30

    Azhar, E. I. et al. Evidence for camel-to-human transmission of MERS coronavirus. N. Engl. J. Med. 370, 2499–2505 (2014).

  31. 31

    Hemida, M. G. et al. MERS coronavirus in dromedary camel herd, Saudi Arabia. Emerg. Infect. Dis. 20, 1231–1234 (2014).

  32. 32

    Raj, V. S. et al. Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014. Emerg. Infect. Dis. 20, 1339–1342 (2014).

  33. 33

    Muller, M. A. et al. MERS coronavirus neutralizing antibodies in camels, Eastern Africa, 1983–1997. Emerg. Infect. Dis. 20, 2093–2095 (2014).

  34. 34

    Sabir, J. S. et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 351, 81–84 (2016).

  35. 35

    Chowell, G. et al. Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study. BMC Med. 13, 210 (2015). An analysis of the predominant role for nosocomial transmission in the epidemiology of both SARS and MERS.

  36. 36

    Hunter, J. C. et al. Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings, Abu Dhabi. Emerg. Infect. Dis. 22, 647–656 (2016).

  37. 37

    Anderson, R. M. et al. Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 359, 1091–1105 (2004).

  38. 38

    Cowling, B. J. et al. Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015. Euro Surveill. 20, 7–13 (2015).

  39. 39

    Peiris, J. S. et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 361, 1767–1772 (2003). A description of the clinical representation of SARS-CoV respiratory disease in patients from Hong Kong.

  40. 40

    Bin, S. Y. et al. Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea. Clin. Infect. Dis. 62, 755–760 (2015). Evidence that infectious MERS-CoV can be detected on common hospital surfaces during an outbreak, which highlights the potential for nosocomial transmission and stresses the need for infection control.

  41. 41

    Kucharski, A. J. & Althaus, C. L. The role of superspreading in Middle East respiratory syndrome coronavirus (MERS-CoV) transmission. Euro Surveill. 20, 14–18 (2015).

  42. 42

    Oh, M. D. et al. Middle East respiratory syndrome coronavirus superspreading event involving 81 persons, Korea 2015. J. Korean Med. Sci. 30, 1701–1705 (2015).

  43. 43

    Wong, G. et al. MERS, SARS, and Ebola: the role of super-spreaders in infectious disease. Cell Host Microbe 18, 398–401 (2015).

  44. 44

    Ng, D. L. et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am. J. Pathol. 186, 652–658 (2016).

  45. 45

    Kuba, K. et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11, 875–879 (2005).

  46. 46

    Imai, Y. et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436, 112–116 (2005).

  47. 47

    Wang, W. K. et al. Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome. Clin. Infect. Dis. 39, 1071–1075 (2004).

  48. 48

    Drosten, C. et al. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect. Dis. 13, 745–751 (2013).

  49. 49

    Poissy, J. et al. Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases. J. Clin. Virol. 61, 275–278 (2014).

  50. 50

    Binnie, A., Tsang, J. L. & dos Santos, C. C. Biomarkers in acute respiratory distress syndrome. Curr. Opin. Crit. Care 20, 47–55 (2014).

  51. 51

    Williams, A. E. & Chambers, R. C. The mercurial nature of neutrophils: still an enigma in ARDS? Am. J. Physiol. Lung Cell. Mol. Physiol. 306, L217–L230 (2014).

  52. 52

    Baas, T., Taubenberger, J. K., Chong, P. Y., Chui, P. & Katze, M. G. SARS-CoV virus–host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues. J. Interferon Cytokine Res. 26, 309–317 (2006).

  53. 53

    Faure, E. et al. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside? PLoS ONE 9, e88716 (2014).

  54. 54

    Kong, S. L., Chui, P., Lim, B. & Salto-Tellez, M. Elucidating the molecular physiopathology of acute respiratory distress syndrome in severe acute respiratory syndrome patients. Virus Res. 145, 260–269 (2009).

  55. 55

    Tang, N. L. et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin. Chem. 51, 2333–2340 (2005).

  56. 56

    Cameron, M. J. et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J. Virol. 81, 8692–8706 (2007).

  57. 57

    Gralinski, L. E. et al. Genome wide identification of SARS-CoV susceptibility loci using the Collaborative Cross. PLoS Genet. 11, e1005504 (2015).

  58. 58

    Jensen, S. & Thomsen, A. R. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J. Virol. 86, 2900–2910 (2012).

  59. 59

    Frieman, M. B. et al. SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism. PLoS Pathog. 6, e1000849 (2010).

  60. 60

    Sheahan, T. et al. MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. PLoS Pathog. 4, e1000240 (2008).

  61. 61

    Zhao, J. et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc. Natl Acad. Sci. USA 111, 4970–4975 (2014). A study in which the DPP4-based host restriction is overcome in mice by expression of the human variant of DPP4, leading to the development of several transgenic mouse models.

  62. 62

    de Wilde, A. H. et al. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. J. Gen. Virol. 94, 1749–1760 (2013).

  63. 63

    Snijder, E. J. et al. Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex. J. Virol. 80, 5927–5940 (2006).

  64. 64

    Bouvet, M. et al. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog. 6, e1000863 (2010).

  65. 65

    Menachery, V. D. et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2′-O-methyltransferase activity. J. Virol. 88, 4251–4264 (2014).

  66. 66

    Menachery, V. D., Debbink, K. & Baric, R. S. Coronavirus non-structural protein 16: evasion, attenuation, and possible treatments. Virus Res. 194, 191–199 (2014).

  67. 67

    Cui, L. et al. The nucleocapsid protein of coronaviruses acts as a viral suppressor of RNA silencing in mammalian cells. J. Virol. 89, 9029–9043 (2015).

  68. 68

    Lu, X., Pan, J., Tao, J. & Guo, D. SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism. Virus Genes 42, 37–45 (2011).

  69. 69

    Niemeyer, D. et al. Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist. J. Virol. 87, 12489–12495 (2013).

  70. 70

    Siu, K. L. et al. Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response. J. Virol. 88, 4866–4876 (2014).

  71. 71

    Yang, Y. et al. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4, 951–961 (2013).

  72. 72

    Yang, Y. et al. Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets. Sci. Rep. 5, 17554 (2015).

  73. 73

    Frieman, M., Ratia, K., Johnston, R. E., Mesecar, A. D. & Baric, R. S. Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-κB signaling. J. Virol. 83, 6689–6705 (2009).

  74. 74

    Devaraj, S. G. et al. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J. Biol. Chem. 282, 32208–32221 (2007).

  75. 75

    Matthews, K., Schafer, A., Pham, A. & Frieman, M. The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity. Virol. J. 11, 209 (2014).

  76. 76

    Bailey-Elkin, B. A. et al. Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression. J. Biol. Chem. 289, 34667–34682 (2014).

  77. 77

    Huang, C. et al. SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLoS Pathog. 7, e1002433 (2011).

  78. 78

    Kamitani, W., Huang, C., Narayanan, K., Lokugamage, K. G. & Makino, S. A two-pronged strategy to suppress host protein synthesis by SARS coronavirus nsp1 protein. Nat. Struct. Mol. Biol. 16, 1134–1140 (2009).

  79. 79

    Tanaka, T., Kamitani, W., DeDiego, M. L., Enjuanes, L. & Matsuura, Y. Severe acute respiratory syndrome coronavirus nsp1 facilitates efficient propagation in cells through a specific translational shutoff of host mRNA. J. Virol. 86, 11128–11137 (2012).

  80. 80

    Wathelet, M. G., Orr, M., Frieman, M. B. & Baric, R. S. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J. Virol. 81, 11620–11633 (2007).

  81. 81

    Lokugamage, K. G. et al. Middle East respiratory syndrome coronavirus nsp1 inhibits host gene expression by selectively targeting mRNAs transcribed in the nucleus while sparing mRNAs of cytoplasmic origin. J. Virol. 89, 10970–10981 (2015).

  82. 82

    Freundt, E. C., Yu, L., Park, E., Lenardo, M. J. & Xu, X. N. Molecular determinants for subcellular localization of the severe acute respiratory syndrome coronavirus open reading frame 3b protein. J. Virol. 83, 6631–6640 (2009).

  83. 83

    Kopecky-Bromberg, S. A., Martinez-Sobrido, L., Frieman, M., Baric, R. A. & Palese, P. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J. Virol. 81, 548–557 (2007).

  84. 84

    Lei, Y. et al. MAVS-mediated apoptosis and its inhibition by viral proteins. PLoS ONE 4, e5466 (2009).

  85. 85

    Menachery, V. D. et al. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. mBio 5, e01174-14 (2014).

  86. 86

    Graci, J. D. & Cameron, C. E. Mechanisms of action of ribavirin against distinct viruses. Rev. Med. Virol. 16, 37–48 (2006).

  87. 87

    Al-Tawfiq, J. A., Momattin, H., Dib, J. & Memish, Z. A. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int. J. Infect. Dis. 20, 42–46 (2014).

  88. 88

    Ling, Y., Qu, R. & Luo, Y. Clinical analysis of the first patient with imported Middle East respiratory syndrome in China. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 27, 630–634 (in Chinese) (2015).

  89. 89

    Booth, C. M. et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 289, 2801–2809 (2003).

  90. 90

    Poutanen, S. M. et al. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 348, 1995–2005 (2003).

  91. 91

    So, L. K. et al. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet 361, 1615–1617 (2003).

  92. 92

    Tsang, K. W. et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 348, 1977–1985 (2003).

  93. 93

    Loutfy, M. R. et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 290, 3222–3228 (2003).

  94. 94

    Zhao, Z. et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J. Med. Microbiol. 52, 715–720 (2003).

  95. 95

    Hsu, L. Y. et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg. Infect. Dis. 9, 713–717 (2003).

  96. 96

    Smith, E. C., Blanc, H., Surdel, M. C., Vignuzzi, M. & Denison, M. R. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLoS Pathog. 9, e1003565 (2013).

  97. 97

    Chan, J. F. et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 67, 606–616 (2013).

  98. 98

    Falzarano, D. et al. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci. Rep. 3, 1686 (2013).

  99. 99

    Hart, B. J. et al. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol. 95, 571–577 (2014).

  100. 100

    Morgenstern, B., Michaelis, M., Baer, P. C., Doerr, H. W. & Cinatl, J. Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem. Biophys. Res. Commun. 326, 905–908 (2005).

  101. 101

    Falzarano, D. et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19, 1313–1317 (2013). The first application of a potential treatment option for MERS through the repurposing of IFNα2b and ribavirin in a non-human primate model.

  102. 102

    Omrani, A. S. et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect. Dis. 14, 1090–1095 (2014).

  103. 103

    Shalhoub, S. et al. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J. Antimicrob. Chemother. 70, 2129–2132 (2015).

  104. 104

    Khalid, M. et al. Ribavirin and interferon-α2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases. Antivir. Ther. 20, 87–91 (2015).

  105. 105

    Chan, J. F. et al. 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. 212, 1904–1913 (2015).

  106. 106

    Chan, K. S. et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med. J. 9, 399–406 (2003).

  107. 107

    Chu, C. M. et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 59, 252–256 (2004).

  108. 108

    Spanakis, N. et al. Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen. Int. J. Antimicrob. Agents 44, 528–532 (2014).

  109. 109

    Choi, W. J., Lee, K. N., Kang, E. J. & Lee, H. Middle East respiratory syndrome-coronavirus infection: a case report of serial computed tomographic findings in a young male patient. Korean J. Radiol 17, 166–170 (2016).

  110. 110

    Kim, U. J., Won, E. J., Kee, S. J., Jung, S. I. & Jang, H. C. Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for Middle East respiratory syndrome: a case report. Antivir. Ther. (2015).

  111. 111

    Rhee, J. Y., Hong, G. & Ryu, K. M. Clinical implications of five cases of Middle East respiratory syndrome coronavirus infection in South Korea Outbreak. Jpn J. Infect. Dis. (2016).

  112. 112

    Hilgenfeld, R. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J. 281, 4085–4096 (2014).

  113. 113

    Cheng, K. W. et al. Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 115, 9–16 (2015).

  114. 114

    Tomar, S. et al. Ligand-induced dimerization of Middle East respiratory syndrome (MERS) coronavirus nsp5 protease (3CLpro): implications for nsp5 regulation and the development of antivirals. J. Biol. Chem. 290, 19403–19422 (2015).

  115. 115

    de Wilde, A. H. et al. 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. 58, 4875–4884 (2014).

  116. 116

    International Severe Acute Respiratory & Emerging Infection Consortium. Treatment of MERS-CoV: decision support tool. International Severe Acute Respiratory & Emerging Infection Consortium, (updated 29 July 2013).

  117. 117

    Mair-Jenkins, J. et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J. Infect. Dis. 211, 80–90 (2015).

  118. 118

    Du, L. et al. A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein. J. Virol. 88, 7045–7053 (2014).

  119. 119

    Jiang, L. et al. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci. Transl Med. 6, 234ra59 (2014).

  120. 120

    Tang, X. C. et al. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc. Natl Acad. Sci. USA 111, E2018–E2026 (2014).

  121. 121

    Ying, T. et al. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88, 7796–7805 (2014).

  122. 122

    Zhao, J. et al. Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection. J. Virol. 89, 6117–6120 (2015).

  123. 123

    Luke, T. et al. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci. Transl Med. 8, 326ra21 (2016).

  124. 124

    Li, Y. et al. A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein. Cell Res. 25, 1237–1249 (2015).

  125. 125

    Corti, D. et al. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. Proc. Natl Acad. Sci. USA 112, 10473–10478 (2015).

  126. 126

    Pascal, K. E. et al. 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. USA 112, 8738–8743 (2015). The first description of the prophylactic and therapeutic efficacy of monoclonal antibodies in a mouse model.

  127. 127

    Houser, K. V. et al. Prophylaxis with a MERS-CoV-specific human monoclonal antibody protects rabbits from MERS-CoV infection. J. Infect. Dis. 213, 1557–1561 (2016).

  128. 128

    Johnson, R. F. et al. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012. Virology 490, 49–58 (2016).

  129. 129

    Ohnuma, K. et al. Inhibition of Middle East respiratory syndrome coronavirus infection by anti-CD26 monoclonal antibody. J. Virol. 87, 13892–13899 (2013).

  130. 130

    Elshabrawy, H. A. et al. Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. J. Virol. 88, 4353–4365 (2014).

  131. 131

    Glowacka, I. et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol. 85, 4122–4134 (2011).

  132. 132

    Zhou, Y. et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 116, 76–84 (2015).

  133. 133

    Wang, R., Xiao, H., Guo, R., Li, Y. & Shen, B. The role of C5a in acute lung injury induced by highly pathogenic viral infections. Emerg. Microbes Infect. 4, e28 (2015).

  134. 134

    Josset, L. et al. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. mBio 4, e00165–13 (2013).

  135. 135

    Graham, R. L., Donaldson, E. F. & Baric, R. S. A decade after SARS: strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 11, 836–848 (2013).

  136. 136

    Roper, R. L. & Rehm, K. E. SARS vaccines: where are we? Expert Rev. Vaccines 8, 887–898 (2009).

  137. 137

    Du, L. & Jiang, S. Middle East respiratory syndrome: current status and future prospects for vaccine development. Expert Opin. Biol. Ther. 15, 1647–1651 (2015).

  138. 138

    Wang, L. et al. Evaluation of candidate vaccine approaches for MERS-CoV. Nat. Commun. 6, 7712 (2015).

  139. 139

    Lan, J. et al. Recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against Middle East respiratory syndrome coronavirus challenge. EBioMedicine 2, 1438–1446 (2015).

  140. 140

    Muthumani, K. et al. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci. Transl Med. 7, 301ra132 (2015).

  141. 141

    Mastalerz-Migas, A., Bujnowska-Fedak, M. & Brydak, L. B. Immune efficacy of first and repeat trivalent influenza vaccine in healthy subjects and hemodialysis patients. Adv. Exp. Med. Biol. 836, 47–54 (2015).

  142. 142

    Muller, M. A. et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect. Dis. 15, 629 (2015).

  143. 143

    Haagmans, B. L. et al. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science 351, 77–81 (2016). The finding that vaccination of dromedary camels reduces MERS-CoV shedding on infection, which provides a proof-of-principle for the vaccination of dromedary camels to block zoonotic transmission.

  144. 144

    Assiri, A. et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 13, 752–761 (2013). A report ofthe clinical presentation of MERS in patients in Saudi Arabia.

  145. 145

    Leung, G. M. et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann. Intern. Med. 141, 662–673 (2004).

  146. 146

    Zumla, A., Hui, D. S. & Perlman, S. Middle East respiratory syndrome. Lancet 386, 995–1007 (2015).

  147. 147

    Al-Abdallat, M. M. et al. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin. Infect. Dis. 59, 1225–1233 (2014).

  148. 148

    Saad, M. et al. 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. 29, 301–306 (2014).

  149. 149

    Memish, Z. A. et al. Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome. J. Infect. Dis. 210, 1590–1594 (2014).

  150. 150

    Feikin, D. R. et al. Association of higher MERS-CoV virus load with severe disease and death, Saudi Arabia, 2014. Emerg. Infect. Dis. 21, 2029–2035 (2015).

  151. 151

    Majumder, M. S., Kluberg, S. A., Mekaru, S. R. & Brownstein, J. S. Mortality risk factors for Middle East respiratory syndrome outbreak, South Korea, 2015. Emerg. Infect. Dis. 21, 2088–2090 (2015).

  152. 152

    Gretebeck, L. M. & Subbarao, K. Animal models for SARS and MERS coronaviruses. Curr. Opin. Virol. 13, 123–129 (2015).

  153. 153

    Munster, V. J. et al. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis). Sci. Rep. 6, 21878 (2016).

  154. 154

    Lau, S. K. et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl Acad. Sci. USA 102, 14040–14045 (2005).

  155. 155

    Li, W. et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 310, 676–679 (2005).

  156. 156

    Wu, D. et al. Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates. J. Virol. 79, 2620–2625 (2005).

  157. 157

    Adney, D. R. et al. Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg. Infect. Dis. 20, 1999–2005 (2014). The first description of MERS-CoV replication and shedding in the respiratory tract of dromedary camels, which suggests that MERS-CoV infects the upper respiratory tract in dromedary camels.

  158. 158

    Becker, M. M. et al. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proc. Natl Acad. Sci. USA 105, 19944–19949 (2008).

  159. 159

    Menachery, V. D. et al. SARS-like WIV1-CoV poised for human emergence. Proc. Natl Acad. Sci. USA 113, 3048–3053 (2016).

Download references


The work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health.

Author information

Correspondence to Vincent J. Munster.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides


Nosocomial transmission

Transmission of an infectious agent by staff, equipment or the environment in a health care setting.


The correction of errors that are acquired during the replication of DNA or RNA.

ER–Golgi intermediate compartment

(ERGIC). A cellular compartment that facilitates transport between the endoplasmic reticulum (ER) and the Golgi complex.

Super spreaders

Infected individuals who each infect a disproportionately large number of secondary cases.

Acute respiratory distress syndrome

(ARDS). A life-threatening condition in which the accumulation of fluid and inflammatory cells in the lungs decreases the exchange of oxygen and carbon dioxide to dangerously low levels.

Collaborative Cross mouse

One of a panel of recombinant inbred mouse strains derived from a genetically diverse set of founder strains and designed for the analysis of complex traits.

Perivascular cuffing

The aggregation of leukocytes around blood vessels.

Type I IFNs

(Type I interferons). A group of IFNs, including IFNα and IFNβ, with immune-modulating and antiviral functions.


A biological process in which small RNA molecules induce the degradation of specific mRNA molecules, thereby inhibiting gene expression.

Minireplicon systems

Systems in which a DNA molecule is produced that contains the viral leader and trailer sequences, with an assayable reporter replacing the viral ORFs. When combined with the expression of viral proteins in trans, this system can be used to model the viral life cycle without the necessity of using infectious virus.


A broadly active antiviral nucleoside analogue with several direct and indirect mechanisms of action; mainly used for the treatment of hepatitis C, in combination with interferon.


Having polyethylene glycol (PEG) attached, to a drug for example; this moiety improves the solubility, decreases the immunogenicity and increases the stability, of the drug of interest, thereby allowing a reduced dosing frequency to be used.


Compounds that mimic biologically active peptides or proteins.

Anaphylatoxin C5a

A complement-activated molecule that is important for the recruitment to and activation of inflammatory cells in the lungs.

Subunit vaccines

Vaccines that contain immunogenic parts of a pathogen rather than the entire pathogen.

DNA vaccines

Vaccines based on the direct introduction of a plasmid encoding an antigen; following in situ production of this antigen, an immune response is mounted against it.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

de Wit, E., van Doremalen, N., Falzarano, D. et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14, 523–534 (2016).

Download citation

Further reading