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==Overview==
==Overview==
[[MERS|Middle East Respiratory Syndrome]] ([[MERS]]) is a [[viral]] [[respiratory disease|respiratory illness]]. It is caused by an emerging [[coronavirus]], specifically a ''betacoronavirus'' called [[Middle east respiratory syndrome coronavirus|MERS-CoV]] ([[Middle east respiratory syndrome coronavirus|Middle East Respiratory Syndrome Coronavirus]]), first discovered in 2012. Potential animal reservoirs and mechanisms of [[transmission]] of [[MERS-CoV]] to [[humans]] remain unclear. Initially a [[zoonotic]] origin for [[MERS-CoV]] was suggested due to the high [[genetic]] similarity to the [[coronavirus|coronaviruses]] in bats. Additionally, recent reports have also described [[serologic]] data similarities in camels and related [[viruses]] have also been identified in bats. However, future studies will have to provide additional [[epidemiologic]] data linking [[human]] [[MERS]] cases to [[infected]] animals in order to determine if a particular [[species]] is a host, a source of [[human]] [[infection]], or both.<ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref><ref name=CDC>{{cite web | title = MERS Prevention and Treatment | url = http://www.cdc.gov/coronavirus/MERS/about/prevention.html }}</ref>
[[MERS-CoV]] has a strong [[tropism]] for the [[cilium|non-ciliated]] [[bronchial]] [[epithelium]]. The [[virus]] has the capacity to evade the [[innate immune system]] and inhibit [[interferon]] production. It uses the DPP4 (or CD26) receptor to bind to the host cell and to release [[viral]] [[nucleocapsid]] into the [[cellular]] [[cytoplasm]]. Once inside the cell, viral replication follows and proteins are expressed. The viral genes encode 4 structural proteins and 5 accessory proteins.  


==Pathophysiology==
==Pathophysiology==
===The Microorganism===
[[MERS|Middle East Respiratory Syndrome]] ([[MERS]]) is a [[viral]] [[respiratory disease|respiratory illness]] caused by an emerging [[coronavirus]], [[MERS|Middle East Respiratory Syndrome Coronavirus]] (MERS-CoV) that was previously known as human betaCoV 2c EMC/2012 (hCoV-EMC).<ref name="pmid23078800">{{cite journal| author=Bermingham A, Chand MA, Brown CS, Aarons E, Tong C, Langrish C et al.| title=Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. | journal=Euro Surveill | year= 2012 | volume= 17 | issue= 40 | pages= 20290 | pmid=23078800 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23078800  }} </ref><ref name="pmid23075143">{{cite journal| author=Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA| title=Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 19 | pages= 1814-20 | pmid=23075143 | doi=10.1056/NEJMoa1211721 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23075143  }} </ref><ref name="pmid23678167">{{cite journal| author=de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L et al.| title=Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. | journal=J Virol | year= 2013 | volume= 87 | issue= 14 | pages= 7790-2 | pmid=23678167 | doi=10.1128/JVI.01244-13 | pmc=PMC3700179 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23678167  }} </ref>  MERS-CoV belongs to the genera betacoronavirus of the family coronaviridae, the largest of all the RNA viruses, with positive single-stranded RNA genomes of 26–32 kilobases.<ref name="pmid23770275">{{cite journal| author=Chan JF, To KK, Tse H, Jin DY, Yuen KY| title=Interspecies transmission and emergence of novel viruses: lessons from bats and birds. | journal=Trends Microbiol | year= 2013 | volume= 21 | issue= 10 | pages= 544-55 | pmid=23770275 | doi=10.1016/j.tim.2013.05.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23770275  }} </ref>  It shares several similarities with SARS-CoV, another betacoronavirus.


===Encounter With the Microorganism===
=== Incubation Period ===


===Colonization===
* The incubation period for MERS infection is 5–7 days, with a range of 2–14 days.<ref name="pmid26049252">{{cite journal |vauthors=Zumla A, Hui DS, Perlman S |title=Middle East respiratory syndrome |journal=Lancet |volume=386 |issue=9997 |pages=995–1007 |date=September 2015 |pmid=26049252 |pmc=4721578 |doi=10.1016/S0140-6736(15)60454-8 |url=}}</ref><ref name="pmid29680581">{{cite journal |vauthors=Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A |title=Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission |journal=Lancet Infect Dis |volume=18 |issue=8 |pages=e217–e227 |date=August 2018 |pmid=29680581 |pmc=7164784 |doi=10.1016/S1473-3099(18)30127-0 |url=}}</ref>
* Immunocompromised patients can present with longer incubation periods of up to 20 days.


===Penetration of Antimicrobial Barrier===
===Cellular Pathogenesis===
*The [[virus]] has the capacity to evade the [[innate immune system]] and inhibit [[interferon]] production.<ref name="Kindler-2013">{{Cite journal|last1=Kindler|first1=E.|last2=Jónsdóttir|first2=H. R.|last3=Muth|first3=D.|last4=Hamming|first4=O. J.|last5=Hartmann|first5=R.|last6=Rodriguez|first6=R.|last7=Geffers|first7=R.|last8=Fouchier|first8=R. A.|last9=Drosten|first9=C.|title=Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential|journal=MBio|volume=4|issue=1|pages=e00611–12|year=2013|doi= 10.1128/mBio.00611-12|pmid=23422412|pmc=3573664|display-authors=9}}</ref><ref name="Raj-2013">{{Cite journal|last1=Raj|first1=V. S.|last2=Mou|first2=H.|last3=Smits|first3=S. L.|last4=Dekkers|first4=D. H.|last5=Müller|first5=M. A.|last6=Dijkman|first6=R.|last7=Muth|first7=D.|last8=Demmers|first8=J. A.|last9=Zaki|first9 = A.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|pages=251–4|date=March 2013|doi=10.1038/nature12005|pmid=23486063|display-authors=9}}</ref>
*Due to the similarities between the [[MERS-CoV]] and the [[SARS-CoV]], it was initially proposed that the [[MERS-CoV]] possible uses the same [[cell receptor|cellular receptor]] for [[infection]], as the [[SARS-CoV]], namely the [[Angiotensin-converting enzyme 2|angiotensin converting enzyme 2]]<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref><ref name="MullerRaj2012">{{cite journal|last1=Muller|first1=M. A.|last2=Raj|first2=V. S.|last3=Muth|first3=D.|last4=Meyer|first4=B.|last5=Kallies|first5=S.|last6=Smits|first6=S. L.|last7=Wollny|first7=R.|last8=Bestebroer|first8=T. M.|last9=Specht|first9=S.|last10=Suliman|first10=T.|last11=Zimmermann|first11=K.|last12=Binger|first12=T.|last13=Eckerle|first13=I.|last14=Tschapka|first14=M.|last15=Zaki|first15=A. M.|last16=Osterhaus|first16=A. D. M. E.|last17=Fouchier|first17=R. A. M.|last18=Haagmans|first18=B. L.|last19=Drosten|first19=C.|title=Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines|journal=mBio|volume=3|issue=6|year=2012|pages=e00515-12–e00515-12|issn=2150-7511|doi=10.1128/mBio.00515-12}}</ref>, however, the [[cell receptor|cellular receptor]] for [[MERS-CoV]] was later identified to be ''dipeptidyl [[peptidase]] 4'' (DDP4) or ''CD26''.<ref name="Raj-2013" />
*The [[amino acid]] sequence of this [[receptor]] is a highly conserved sequence across [[species]], being expressed in human [[bronchial]] [[epithelium]] and [[kidneys]], and its [[enzymatic]] activity is not required for the process of [[infection]].<ref name="Raj-2013" /><ref name="dpp4_receptor">{{cite web|title=Receptor for new coronavirus found|url=http://www.nature.com/news/receptor-for-new-coronavirus-found-1.12584|date=2013-03-13|accessdate=2013-03-18|publisher=nature.com}}</ref>
*DDP4 is a [[neutrophil]] [[chemorepellent]]. Its loss from the [[cell membrane|cell surface]] results in [[cellular]] alteration of the composition of the [[immune cell]] infiltrate and subsequent alteration of the natural history of the [[infectious]] state.<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="pmid20134095">{{cite journal| author=Imai Y, Kuba K, Ohto-Nakanishi T, Penninger JM| title=Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. | journal=Circ J | year= 2010 | volume= 74 | issue= 3 | pages= 405-10 | pmid=20134095 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20134095  }} </ref><ref name="pmid12892317">{{cite journal| author=Lambeir AM, Durinx C, Scharpé S, De Meester I| title=Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. | journal=Crit Rev Clin Lab Sci | year= 2003 | volume= 40 | issue= 3 | pages= 209-94 | pmid=12892317 | doi=10.1080/713609354 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12892317  }} </ref><ref name="pmid23677473">{{cite journal| author=Herlihy SE, Pilling D, Maharjan AS, Gomer RH| title=Dipeptidyl peptidase IV is a human and murine neutrophil chemorepellent. | journal=J Immunol | year= 2013 | volume= 190 | issue= 12 | pages= 6468-77 | pmid=23677473 | doi=10.4049/jimmunol.1202583 | pmc=PMC3756559 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23677473  }} </ref>
*When [[MERS-CoV]] binds to its [[cellular]] [[receptor]], a series of reactions involving host [[proteases]], such as [[cathepsin B]], are triggered. These include the excision of the surface [[glycoprotein]], which will ultimately:<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="GiererBertram2013">{{cite journal|last1=Gierer|first1=S.|last2=Bertram|first2=S.|last3=Kaup|first3=F.|last4=Wrensch|first4=F.|last5=Heurich|first5=A.|last6=Kramer-Kuhl|first6=A.|last7=Welsch|first7=K.|last8=Winkler|first8=M.|last9=Meyer|first9=B.|last10=Drosten|first10=C.|last11=Dittmer|first11=U.|last12=von Hahn|first12=T.|last13=Simmons|first13=G.|last14=Hofmann|first14=H.|last15=Pohlmann|first15=S.|title=The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies|journal=Journal of Virology|volume=87|issue=10|year=2013|pages=5502–5511|issn=0022-538X|doi=10.1128/JVI.00128-13}}</ref>
*Expose fusion [[peptide]]
*Allow fusion between [[virus]] and [[cell membrane]]
*Lead to the release of the [[viral]] [[nucleocapsid]] into [[cellular]] [[cytoplasm]]


===Spread===
===Genome===
The betacoronavirus contains a [[genome]] composed of 30,119 [[nucleotides]] that encodes structural and non-structural [[proteins]]. The genome is considered the largest among all RNA virus genomes, reaching 27-32 kb in size.


===Mechanism of Damage===
===Protein Expression ===
The structural [[proteins]] expressed by the betacoronavirus include:<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="van Boheemende Graaf2012">{{cite journal|last1=van Boheemen|first1=S.|last2=de Graaf|first2=M.|last3=Lauber|first3=C.|last4=Bestebroer|first4=T. M.|last5=Raj|first5=V. S.|last6=Zaki|first6=A. M.|last7=Osterhaus|first7=A. D. M. E.|last8=Haagmans|first8=B. L.|last9=Gorbalenya|first9=A. E.|last10=Snijder|first10=E. J.|last11=Fouchier|first11=R. A. M.|title=Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans|journal=mBio|volume=3|issue=6|year=2012|pages=e00473-12–e00473-12|issn=2150-7511|doi=10.1128/mBio.00473-12}}</ref>
*1 [[Nucleocapsid]] (N) protein is required for encapsidation and [[viral replication]]
*1 [[Glycoprotein]] is required for viral entry into the host cell
*2 [[membrane proteins]] required for [[viral]] structure and assembly
All 4 structural proteins are encoded by genes located at the 3' end of the RNA chain. In addition to the 4 structural proteins, the genome encodes 5 accessory proteins involved in viral assembly and evasion of the host immune system.<ref name="NarayananHuang2008">{{cite journal|last1=Narayanan|first1=Krishna|last2=Huang|first2=Cheng|last3=Makino|first3=Shinji|title=SARS coronavirus accessory proteins|journal=Virus Research|volume=133|issue=1|year=2008|pages=113–121|issn=01681702|doi=10.1016/j.virusres.2007.10.009}}</ref><ref name="van Boheemende Graaf2012">{{cite journal|last1=van Boheemen|first1=S.|last2=de Graaf|first2=M.|last3=Lauber|first3=C.|last4=Bestebroer|first4=T. M.|last5=Raj|first5=V. S.|last6=Zaki|first6=A. M.|last7=Osterhaus|first7=A. D. M. E.|last8=Haagmans|first8=B. L.|last9=Gorbalenya|first9=A. E.|last10=Snijder|first10=E. J.|last11=Fouchier|first11=R. A. M.|title=Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans|journal=mBio|volume=3|issue=6|year=2012|pages=e00473-12–e00473-12|issn=2150-7511|doi=10.1128/mBio.00473-12}}</ref>


===Resolution===
===Tropism===
* [[MERS-CoV]] has a strong [[tropism]] for the [[cilium|non-ciliated]] [[bronchial]] [[epithelium]].
* Less commonly, MERS-CoV may primarily infect cells of the GI tract or the neurological system.
 
===Transmission===
* MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans.
* Although bats are the natural host of the betacoronavirus, it is unknown if MERS coronavirus transmission to humans is through bats, through an intermediate animal hosts following crossover and subsequent adaptation, or through a completely different host.
* Limited data is available to confirm or rule out human-to-human transmission.
 
== Associated Conditions ==
 
* Co-infection of MERS-CoV with other respiratory viruses such as:<ref name="pmid28177862">{{cite journal |vauthors=Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK, Al-Omari A, Hajeer AH, Senga M, Denison MR, Nguyen-Van-Tam JS, Shindo N, Bermingham A, Chappell JD, Van Kerkhove MD, Fowler RA |title=Middle East Respiratory Syndrome |journal=N. Engl. J. Med. |volume=376 |issue=6 |pages=584–594 |date=February 2017 |pmid=28177862 |pmc=5362064 |doi=10.1056/NEJMsr1408795 |url=}}</ref>
** [[Parainfluenza virus]]
** [[Rhinovirus]]
** [[Influenza A virus|Influenza A]] or [[Influenza B virus|B virus]]
** [[Respiratory syncytial virus]]
** [[Enteroviruses]]
** [[Human metapneumovirus]]
** [[Nosocomial infection|Nosocomial bacterial infections]].


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

MERS-CoV has a strong tropism for the non-ciliated bronchial epithelium. The virus has the capacity to evade the innate immune system and inhibit interferon production. It uses the DPP4 (or CD26) receptor to bind to the host cell and to release viral nucleocapsid into the cellular cytoplasm. Once inside the cell, viral replication follows and proteins are expressed. The viral genes encode 4 structural proteins and 5 accessory proteins.

Pathophysiology

Incubation Period

  • The incubation period for MERS infection is 5–7 days, with a range of 2–14 days.[1][2]
  • Immunocompromised patients can present with longer incubation periods of up to 20 days.

Cellular Pathogenesis

Genome

The betacoronavirus contains a genome composed of 30,119 nucleotides that encodes structural and non-structural proteins. The genome is considered the largest among all RNA virus genomes, reaching 27-32 kb in size.

Protein Expression

The structural proteins expressed by the betacoronavirus include:[5][13]

All 4 structural proteins are encoded by genes located at the 3' end of the RNA chain. In addition to the 4 structural proteins, the genome encodes 5 accessory proteins involved in viral assembly and evasion of the host immune system.[14][13]

Tropism

Transmission

  • MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans.
  • Although bats are the natural host of the betacoronavirus, it is unknown if MERS coronavirus transmission to humans is through bats, through an intermediate animal hosts following crossover and subsequent adaptation, or through a completely different host.
  • Limited data is available to confirm or rule out human-to-human transmission.

Associated Conditions

References

  1. ↑ Zumla A, Hui DS, Perlman S (September 2015). "Middle East respiratory syndrome". Lancet. 386 (9997): 995–1007. doi:10.1016/S0140-6736(15)60454-8. PMC 4721578. PMID 26049252.
  2. ↑ Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A (August 2018). "Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission". Lancet Infect Dis. 18 (8): e217–e227. doi:10.1016/S1473-3099(18)30127-0. PMC 7164784 Check |pmc= value (help). PMID 29680581.
  3. ↑ Kindler, E.; Jónsdóttir, H. R.; Muth, D.; Hamming, O. J.; Hartmann, R.; Rodriguez, R.; Geffers, R.; Fouchier, R. A.; Drosten, C. (2013). "Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential". MBio. 4 (1): e00611–12. doi:10.1128/mBio.00611-12. PMC 3573664. PMID 23422412.
  4. ↑ 4.0 4.1 4.2 Raj, V. S.; Mou, H.; Smits, S. L.; Dekkers, D. H.; Müller, M. A.; Dijkman, R.; Muth, D.; Demmers, J. A.; Zaki, A. (March 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. 495 (7440): 251–4. doi:10.1038/nature12005. PMID 23486063.
  5. ↑ 5.0 5.1 5.2 5.3 Perlman, S. (2013). "The Middle East Respiratory Syndrome--How Worried Should We Be?". mBio. 4 (4): e00531–13–e00531–13. doi:10.1128/mBio.00531-13. ISSN 2150-7511.
  6. ↑ Raj, V. Stalin; Mou, Huihui; Smits, Saskia L.; Dekkers, Dick H. W.; Müller, Marcel A.; Dijkman, Ronald; Muth, Doreen; Demmers, Jeroen A. A.; Zaki, Ali; Fouchier, Ron A. M.; Thiel, Volker; Drosten, Christian; Rottier, Peter J. M.; Osterhaus, Albert D. M. E.; Bosch, Berend Jan; Haagmans, Bart L. (2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. 495 (7440): 251–254. doi:10.1038/nature12005. ISSN 0028-0836.
  7. ↑ Muller, M. A.; Raj, V. S.; Muth, D.; Meyer, B.; Kallies, S.; Smits, S. L.; Wollny, R.; Bestebroer, T. M.; Specht, S.; Suliman, T.; Zimmermann, K.; Binger, T.; Eckerle, I.; Tschapka, M.; Zaki, A. M.; Osterhaus, A. D. M. E.; Fouchier, R. A. M.; Haagmans, B. L.; Drosten, C. (2012). "Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines". mBio. 3 (6): e00515–12–e00515–12. doi:10.1128/mBio.00515-12. ISSN 2150-7511.
  8. ↑ "Receptor for new coronavirus found". nature.com. 2013-03-13. Retrieved 2013-03-18.
  9. ↑ Imai Y, Kuba K, Ohto-Nakanishi T, Penninger JM (2010). "Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis". Circ J. 74 (3): 405–10. PMID 20134095.
  10. ↑ Lambeir AM, Durinx C, Scharpé S, De Meester I (2003). "Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV". Crit Rev Clin Lab Sci. 40 (3): 209–94. doi:10.1080/713609354. PMID 12892317.
  11. ↑ Herlihy SE, Pilling D, Maharjan AS, Gomer RH (2013). "Dipeptidyl peptidase IV is a human and murine neutrophil chemorepellent". J Immunol. 190 (12): 6468–77. doi:10.4049/jimmunol.1202583. PMC 3756559. PMID 23677473.
  12. ↑ Gierer, S.; Bertram, S.; Kaup, F.; Wrensch, F.; Heurich, A.; Kramer-Kuhl, A.; Welsch, K.; Winkler, M.; Meyer, B.; Drosten, C.; Dittmer, U.; von Hahn, T.; Simmons, G.; Hofmann, H.; Pohlmann, S. (2013). "The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies". Journal of Virology. 87 (10): 5502–5511. doi:10.1128/JVI.00128-13. ISSN 0022-538X.
  13. ↑ 13.0 13.1 van Boheemen, S.; de Graaf, M.; Lauber, C.; Bestebroer, T. M.; Raj, V. S.; Zaki, A. M.; Osterhaus, A. D. M. E.; Haagmans, B. L.; Gorbalenya, A. E.; Snijder, E. J.; Fouchier, R. A. M. (2012). "Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans". mBio. 3 (6): e00473–12–e00473–12. doi:10.1128/mBio.00473-12. ISSN 2150-7511.
  14. ↑ Narayanan, Krishna; Huang, Cheng; Makino, Shinji (2008). "SARS coronavirus accessory proteins". Virus Research. 133 (1): 113–121. doi:10.1016/j.virusres.2007.10.009. ISSN 0168-1702.
  15. ↑ Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK, Al-Omari A, Hajeer AH, Senga M, Denison MR, Nguyen-Van-Tam JS, Shindo N, Bermingham A, Chappell JD, Van Kerkhove MD, Fowler RA (February 2017). "Middle East Respiratory Syndrome". N. Engl. J. Med. 376 (6): 584–594. doi:10.1056/NEJMsr1408795. PMC 5362064. PMID 28177862.

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