Coronaviruses are important human and animal pathogens causing respiratory and gastrointestinal infections ranging from mild to severe. Two highly pathogenic human coronaviruses with high fatality rates, SARS‐CoV and MERS‐CoV, have emerged in different parts of the world in the recent past causing major public health concerns. Several unique features of coronaviruses make them likely the candidates for zoonotic transmissions into the human population: (1) their exceptionally large RNA genomes allow for increased plasticity and diversity, (2) their presence in mammalian (bat) and avian reservoir species with specialised immune functions and increased mobility facilitates their geographical spread and (3) their sophisticated molecular mechanisms of viral entry, replication and assembly involving a number of poorly studied viral accessory proteins complicates the development of suitable therapeutic strategies.

Key Concepts

  • Coronaviruses contain the largest known viral RNA genomes.
  • Bats and birds are major reservoirs for coronaviruses.
  • Two highly pathogenic human coronaviruses, SARS‐CoV and MERS‐CoV, have emerged since the early 2000s.
  • Coronavirus spike proteins are activated by a variety of proteases, often in a two‐step proteolysis process.
  • Many coronaviruses utilise exopeptidases as primary cellular receptors.

Keywords: β‐coronaviruses; SARS coronavirus (SARS‐CoV); Middle East respiratory syndrome coronavirus (MERS‐CoV); viral entry; viral assembly; viral replication

Figure 1. Phylogenetic relationships between selected coronaviruses. Molecular Phylogenetic analysis of full‐length coronavirus RNA‐dependent RNA polymerase sequences by Maximum Likelihood method. The evolutionary history was inferred by using the Maximum Likelihood method based on the JTT matrix‐based model. The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analysed. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbour‐Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log‐likelihood value. The analysis involved 29 amino acid sequences. All positions containing gaps and missing data were eliminated. There were a total of 910 positions in the final dataset. Evolutionary analyses were conducted in MEGA6. For references, see: Jones, D.T., et al., 1992. The rapid generation of mutation data matrices from protein sequences. Computer Applications in the Biosciences: CABIOS 8, 275–282 and Tamura, K., et al., 2013. MEGA6: Molecular Evolutionary Genetics Analysis, version 6.0. Molecular Biology and Evolution 30, 2725–2729.
Figure 2. Schematic representation of coronavirus transmission cycles. The coronavirus genera ‐ and β‐coronaviruses originate from bats and infect a number of different mammalian species including humans either directly or through intermediate hosts. In contrast, the genera γ‐ and ‐coronavirus have evolved separately and are maintained in avian reservoir species and only few mammalian host species have been identified thus far.
Figure 3. (a) Transmission electron micrograph (TEM) of a number of infectious bronchitis virus (IBV) virions, which are family members, and members of the genus Coronavirus. The coronavirus derives its name from the fact that under electron microscopic examination, each virion is surrounded by a ‘corona’ or halo. This is due to the presence of viral spike peplomers emanating from its proteinaceous capsid. (Content providers: Dr. Fred Murphy and Sylvia Whitfield (CDC). This image is in the public domain and thus free of any copyright restrictions.) (b) Schematic representation of a murine hepatitis virus particle. The single‐stranded, positive‐sense RNA genome in complex with the nucleocapsid protein (N) is packaged into the core of the particle, while the hemagglutinin esterase (HE), spike (S), small envelope (E) and membrane (M) proteins are embedded into the host cell‐derived membranous envelope.


Belouzard S, Millet JK, Licitra BN and Whittaker GR (2012) Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4: 1011–1033.

Chan JF, To KK, Tse H, Jin DY and Yuen KY (2013) Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Trends in Microbiology 21: 544–555.

Cologna R and Hogue BG (2000) Identification of a bovine coronavirus packaging signal. Journal of Virology 74: 580–583.

de Haan CA, Vennema H and Rottier PJ (2000) Assembly of the coronavirus envelope: homotypic interactions between the M proteins. Journal of Virology 74: 4967–4978.

de Haan CA, Haijema BJ, Schellen P, et al. (2008) Cleavage of group 1 coronavirus spike proteins: how furin cleavage is traded off against heparan sulfate binding upon cell culture adaptation. Journal of Virology 82: 6078–6083.

Dong BQ, Liu W, Fan XH, et al. (2007) Detection of a novel and highly divergent coronavirus from Asian leopard cats and Chinese ferret badgers in Southern China. Journal of Virology 81: 6920–6926.

Fu K and Baric RS (1994) Map locations of mouse hepatitis virus temperature‐sensitive mutants: confirmation of variable rates of recombination. Journal of Virology 68: 7458–7466.

Ge XY, Li JL, Yang XL, et al. (2013) Isolation and characterization of a bat SARS‐like coronavirus that uses the ACE2 receptor. Nature 503: 535–538.

Glowacka I, Bertram S, Herzog P, et al. (2010) Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. Journal of Virology 84: 1198–1205.

Godeke GJ, de Haan CA, Rossen JW, Vennema H and Rottier PJ (2000) Assembly of spikes into coronavirus particles is mediated by the carboxy‐terminal domain of the spike protein. Journal of Virology 74: 1566–1571.

Graham RL and Baric RS (2010) Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross‐species transmission. Journal of Virology 84: 3134–3146.

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

Haagmans BL, Al Dhahiry SH, Reusken CB, et al. (2014) Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. The Lancet Infectious Diseases 14: 140–145.

Herrewegh AA, Smeenk I, Horzinek MC, Rottier PJ and de Groot RJ (1998) Feline coronavirus type II strains 79–1683 and 79–1146 originate from a double recombination between feline coronavirus type I and canine coronavirus. Journal of Virology 72: 4508–4514.

Heusipp G, Grötzinger C, Herold J, Siddell SG and Ziebuhr J (1997) Identification and subcellular localization of a 41 kDa, polyprotein 1ab processing product in human coronavirus 229E‐infected cells. The Journal of General Virology 78 (Pt 11): 2789–2794.

Hofmann H, Pyrc K, van der Hoek L, et al. (2005) Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proceedings of the National Academy of Sciences of the United States of America 102: 7988–7993.

Hofmann H and Pohlmann S (2011) DC‐SIGN: access portal for sweet viral killers. Cell Host & Microbe 10: 5–7.

Huang Y, Yang ZY, Kong WP and Nabel GJ (2004) Generation of synthetic severe acute respiratory syndrome coronavirus pseudoparticles: implications for assembly and vaccine production. Journal of Virology 78: 12557–12565.

Hurst KR, Kuo L, Koetzner CA, et al. (2005) A major determinant for membrane protein interaction localizes to the carboxy‐terminal domain of the mouse coronavirus nucleocapsid protein. Journal of Virology 79: 13285–13297.

Jeffers SA, Hemmila EM and Holmes KV (2006) Human coronavirus 229E can use CD209L (L‐SIGN) to enter cells. Advances in Experimental Medicine and Biology 581: 265–269.

Krempl C, Schultze B, Laude H and Herrler G (1997) Point mutations in the S protein connect the sialic acid binding activity with the enteropathogenicity of transmissible gastroenteritis coronavirus. Journal of Virology 71: 3285–3287.

Kuo L, Koetzner CA, Hurst KR and Masters PS (2014) Recognition of the murine coronavirus genomic RNA packaging signal depends on the second RNA‐binding domain of the nucleocapsid protein. Journal of Virology 88: 4451–4465.

Lau SK, Lee P and Tsang AK (2011) Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. Journal of Virology 85: 11325–11337.

Li W, Moore MJ, Vasilieva N, et al. (2003) Angiotensin‐converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426: 450–454.

Madu IG, Chu VC, Lee H, et al. (2007) Heparan sulfate is a selective attachment factor for the avian coronavirus infectious bronchitis virus Beaudette. Avian Diseases 51: 45–51.

Marzi A, Gramberg T, Simmons G, et al. (2004) DC‐SIGN and DC‐SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. Journal of Virology 78: 12090–12095.

Millet JK and Whittaker GR (2014) Host cell entry of Middle East respiratory syndrome coronavirus after two‐step, furin‐mediated activation of the spike protein. Proceedings of the National Academy of Sciences of the United States of America 111: 15214–15219.

Miura TA, Travanty EA, Oko L, et al. (2008) The spike glycoprotein of murine coronavirus MHV‐JHM mediates receptor‐independent infection and spread in the central nervous systems of Ceacam1a−/− Mice. Journal of Virology 82: 755–763.

Peiris JS, Guan Y and Yuen KY (2004) Severe acute respiratory syndrome. Nature Medicine 10: S88–S97.

Raj VS, Mou H, Smit SL, et al. (2013) Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus‐EMC. Nature 495: 251–254.

Regan AD and Whittaker GR (2008) Utilization of DC‐SIGN for entry of feline coronaviruses into host cells. Journal of Virology 82: 11992–11996.

Reguera J, Santiago C, Mudgal G, et al. (2012) Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies. PLoS Pathogens 8: e1002859.

Reusken CB, Haagmans BL, Muller MA, et al. (2013) Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. The Lancet Infectious Diseases 13: 859–866.

Sharif‐Yakan A and Kanj SS (2014) Emergence of MERS‐CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives. PLoS Pathogens 10: e1004457.

Shi Z and Hu Z (2008) A review of studies on animal reservoirs of the SARS coronavirus. Virus Research 133: 74–87.

Simmons G, Reeves JD, Rennekamp AJ, et al. (2004) Characterization of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) spike glycoprotein‐mediated viral entry. Proceedings of the National Academy of Sciences of the United States of America 101: 4240–4245.

Simmons G, Gosalia DN, Rennekamp AJ, et al. (2005) Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proceedings of the National Academy of Sciences of the United States of America 102: 11876–11881.

Song D and Park B (2012) Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines. Virus Genes 44: 167–175.

Stevenson GW, Hoang H, Schwartz K, et al. (2013) Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences. Journal of Veterinary Diagnostic Investigation 25: 649–654.

Tusell SM, Schittone SA and Holmes KV (2007) Mutational analysis of aminopeptidase N, a receptor for several group 1 coronaviruses, identifies key determinants of viral host range. Journal of Virology 81: 1261–1273.

van Boheemen S, de Graaf M, Lauber C, et al. (2012) Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 3 (6): e00473‐12.

van der Hoek L, Pyrc K, Jebbink MF, et al. (2004) Identification of a new human coronavirus. Nature Medicine 10: 368–373.

van der Meer Y, van Tol H, Krijnse Locker J and Snijder EJ (1998) ORF1a‐encoded replicase subunits are involved in the membrane association of the arterivirus replication complex. Journal of Virology 72: 6689–6698.

Vennema H, Godeke GJ, Rossen JW, et al. (1996) Nucleocapsid‐independent assembly of coronavirus‐like particles by co‐expression of viral envelope protein genes. The EMBO Journal 15: 2020–2028.

Winter C, Schwegmann‐Wessels C, Cavanagh D, Neumann U and Herrler G (2006) Sialic acid is a receptor determinant for infection of cells by avian Infectious bronchitis virus. The Journal of General Virology 87: 1209–1216.

Woo PC, Lau SK, Chu CM, et al. (2005) Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. Journal of Virology 79: 884–895.

Woo PC, Lau SK, Lam CS, et al. (2012) Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. Journal of Virology 86: 3995–4008.

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD and Fouchier RA (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. The New England Journal of Medicine 367: 1814–1820.

Zhang Y, Buckles E and Whittaker GR (2012) Expression of the C‐type lectins DC‐SIGN or L‐SIGN alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus. Veterinary Microbiology 157: 285–293.

Further Reading

Brian DA and Baric RS (2005) Coronavirus genome structure and replication. Current Topics in Microbiology and Immunology 287: 1–30.

Coleman CM and Frieman MB (2014) Coronaviruses: important emerging human pathogens. Journal of Virology 88: 5209–5212.

Graham RL, Donaldson EF and Baric RS (2013) A decade after SARS: strategies for controlling emerging coronaviruses. Nature Reviews. Microbiology 11: 836–848.

Masters PS (2006) The molecular biology of coronaviruses. Advances in Virus Research 66: 193–292.

Totura AL and Baric RS (2012) SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Current Opinion in Virology 2: 264–275.

Woo PC, Lau SK, Huang Y and Yuen KY (2009) Coronavirus diversity, phylogeny and interspecies jumping. Experimental Biology and Medicine (Maywood, N.J.) 234: 1117–1127.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Steffen, Imke, and Simmons, Graham(Jul 2015) Coronaviruses. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023611]