Middle East respiratory syndrome coronavirus

This article is about the virus. For the disease, see Middle East respiratory syndrome.
MERS-CoV
MERS-CoV particles as seen by negative stain electron microscopy. Virions contain characteristic club-like projections emanating from the viral membrane.
Virus classification
Group: Group IV ((+)ssRNA)
Order: Nidovirales
Family: Coronaviridae
Subfamily: Coronavirinae
Genus: Betacoronavirus
Species: MERS-CoV

The Middle East respiratory syndrome coronavirus (MERS-CoV),[1] or EMC/2012 (HCoV-EMC/2012), is a novel positive-sense, single-stranded RNA virus of the genus Betacoronavirus.

Initially called novel coronavirus 2012 or simply novel coronavirus, it was first reported in 2012 after genome sequencing of a virus isolated from sputum samples from a person who fell ill in a 2012 outbreak of a new flu.

As of July 2015, MERS-CoV cases have been reported in over 21 countries, including Saudi Arabia, Jordan, Qatar, Egypt, the United Arab Emirates, Kuwait, Turkey, Oman, Algeria, Bangladesh, Indonesia (none were confirmed), Austria,[2] the United Kingdom, South Korea,[3][4] the United States,[5][6] Mainland China,[7] Thailand,[8] and the Philippines.[9]

Virology

The virus MERS-CoV is a new member of the beta group of coronavirus, Betacoronavirus, lineage C. MERS-CoV genomes are phylogenetically classified into two clades, clade A and B. The earliest cases of MERS were of clade A clusters (EMC/2012 and Jordan-N3/2012), and new cases are genetically distinct (clade B).[10]

MERS-CoV is distinct from SARS coronavirus and distinct from the common-cold coronavirus and known endemic human betacoronaviruses HCoV-OC43 and HCoV-HKU1.[11] Until 23 May 2013, MERS-CoV had frequently been referred to as a SARS-like virus,[12] or simply the novel coronavirus, and early it was referred to colloquially on messageboards as the "Saudi SARS".

Middle East respiratory syndrome coronavirus 3-D image

Over 1,600 cases of MERS have been reported by 2015 and the case fatality rate is >30%.[13] 182 genomes have been sequenced by 2015 (94 from humans and 88 from dromedary camels). All sequences are >99% similar. The genomes can be divided into two clades - A and B - with the majority of cases being cased by clade B. Human and camel strains are intermixed suggesting multiple transmission events.

Origin

The first confirmed case was reported in Saudi Arabia in 2012.[11] Egyptian virologist Dr. Ali Mohamed Zaki isolated and identified a previously unknown coronavirus from the man's lungs.[14][15][16] Dr. Zaki then posted his findings on 24 September 2012 on ProMED-mail.[15][17][17] The isolated cells showed cytopathic effects (CPE), in the form of rounding and syncytia formation.[17]

A second case was found in September 2012, a 49-year-old male living in Qatar presented with similar flu symptoms, and a sequence of the virus was nearly identical to that of the first case.[11] In November 2012, similar cases appeared in Qatar and Saudi Arabia. Additional cases were noted, with deaths associated, and rapid research and monitoring of this novel coronavirus began.

It is not certain whether the infections are the result of a single zoonotic event with subsequent human-to-human transmission, or if the multiple geographic sites of infection represent multiple zoonotic events from a common unknown source.

A study by Ziad Memish of Riyadh University and colleagues suggests that the virus arose sometime between July 2007 and June 2012, with perhaps as many as 7 separate zoonotic transmissions. Among animal reservoirs, CoV has a large genetic diversity yet the samples from patients suggest a similar genome, and therefore common source, though the data are limited. It has been determined through molecular clock analysis, that viruses from the EMC/2012 and England/Qatar/2012 date to early 2011 suggesting that these cases are descended from a single zoonotic event. It would appear the MERS-CoV has been circulating in the human population for greater than one year without detection and suggests independent transmission from an unknown source.[18][19]

Tropism

In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells.[20][21]

Due to the clinical similarity between MERS-CoV and SARS-CoV, it was proposed that they may use the same cellular receptor; the exopeptidase, angiotensin converting enzyme 2 (ACE2).[22] However, it was later discovered that neutralization of ACE2 by recombinant antibodies does not prevent MERS-CoV infection.[23] Further research identified dipeptyl peptidase 4 (DPP4; also known as CD26) as a functional cellular receptor for MERS-CoV.[21] Unlike other known coronavirus receptors, the enzymatic activity of DPP4 is not required for infection. As would be expected, the amino acid sequence of DPP4 is highly conserved across species and is expressed in the human bronchial epithelium and kidneys.[21][24] Bat DPP4 genes appear to have been subject to a high degree of adaptive evolution as a response to coronavirus infections, so the lineage leading to MERS-CoV may have circulated in bat populations for a long period of time before being transmitted to people.[25]

Transmission

On 13 February 2013, the World Health Organization stated "the risk of sustained person-to-person transmission appears to be very low."[26] The cells MERS-CoV infects in the lungs only account for 20% of respiratory epithelial cells, so a large number of virions are likely needed to be inhaled to cause infection.[24]

Dr. Anthony S. Fauci of the National Institutes of Health in Bethesda, Maryland, stated that as of now MERS-CoV "does not spread in a sustained person to person way at all." Dr. Fauci stated that there is potential danger in that it is possible for the virus to mutate into a strain that does transmit from person to person.[27]

However, the infection of healthcare workers (HCW) has led to concerns of human to human transmission.[28]

The Centers for Disease Control and Prevention (CDC) list MERS as transmissible from human-to-human. From their FAQ, in answer to the question "Does MERS-CoV spread from person to person?", they answer "MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed. Clusters of cases in several countries are being investigated."[29] There is also a New York Times article which provides some correlative context for this.[30]

However, on the 28th of May, the CDC revealed that the Illinois man who was originally thought to have been the first incidence of person to person spread (from the Indiana man at a business meeting), had in fact tested negative for MERS-CoV. After completing additional and more definitive tests using a neutralising antibody assay, experts at the CDC have concluded that the Indiana patient did not spread the virus to the Illinois patient. Tests concluded that the Illinois man had not been previously infected. It is possible for silent MERS to occur, this is when the patient does not develop symptoms. Early research has shown that up to 20% of cases show no signs of active infection but have MERS-CoV antibodies in their blood.[31]

Evolution

The virus appears to have originated in bats.[32] The virus itself has been isolated from a bat.[33] This virus is closely related to the Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5.[34] Serological evidence shows that these viruses have infected camels for at least 20 years. The most recent common ancestor of several human strains has been dated to March 2012 (95% confidence interval December 2011 to June 2012).[35]

The evidence available to date suggests that the viruses have been present in bats for some time and had spread to camels by the mid 1990s. The viruses appear to have spread from camels to humans in the early 2010s. The original bat host species and the time of initial infection in this species has yet to be determined.

Natural reservoir

Early research suggested the virus is related to one found in the Egyptian tomb bat. In September 2012 Ron Fouchier speculated that the virus might have originated in bats.[36] Work by epidemiologist Ian Lipkin of Columbia University in New York showed that the virus isolated from a bat looked to be a match to the virus found in humans.[37][38][39] 2c betacoronaviruses were detected in Nycteris bats in Ghana and Pipistrellus bats in Europe that are phylogenetically related to the MERS-CoV virus.[40] However the major natural reservoir where humans get the virus infection remained unknown until on 9 August 2013, a report in the journal The Lancet Infectious Diseases showed that 50 out of 50 (100%) blood serum from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against the MERS-CoV spike protein. Blood serum from European sheep, goats, cattle, and other camelids had no such antibodies.[41]

Soon after on 5 September 2013 a seroepidemiological study published in the journal of Eurosurveillance by R.A Perera et al[42] where they investigated 1343 human and 625 animal sera indicated, the abundant presence of MERS-CoV specific antibody in 108 out of 110 Egyptian dromedary camels but not in other animals such as goats, cows or sheep in this region.[42] These are the first and significant scientific reports that indicated the role of "dromedary camels" as a reservoir of MERS-CoV.

Recent work links camels to the virus. An ahead-of-print dispatch for the journal Emerging Infectious Diseases records research showing the coronavirus infection in dromedary camel calves and adults, 99.9% matching to the genomes of human clade B MERS-CoV.[43]

At least one person who has fallen sick with MERS was known to have come into contact with camels or recently drank camel milk.[44]

Countries like Saudi Arabia and the United Arab Emirates produce and consume large amounts of camel meat. The possibility exists that African or Australian bats harbor the virus and transmit it to camels. Imported camels from these regions might have carried the virus to the Middle East.[45]

In 2013 MERS-CoV was identified in three members of a dromedary camel herd held in a Qatar barn, which was linked to two confirmed human cases who have since recovered. The presence of MERS-CoV in the camels was confirmed by the National Institute of Public Health and Environment (RIVM) of the Ministry of Health and the Erasmus Medical Center (WHO Collaborating Center), the Netherlands. None of the camels showed any sign of disease when the samples were collected. The Qatar Supreme Council of Health advised in November 2013 that people with underlying health conditions, such as heart disease, diabetes, kidney disease, respiratory disease, the immunosuppressed, and the elderly, avoid any close animal contacts when visiting farms and markets, and to practice good hygiene, such as washing hands.[46]

A further study on dromedary camels from Saudi Arabia published in December 2013 revealed the presence of MERS-CoV in 90% of the evaluated dromedary camels (310), suggesting that dromedary camels not only could be the main reservoir of MERS-CoV, but also the animal source of MERS.[47]

According to the 27 March 2014 MERS-CoV summary update, recent studies support that camels serve as the primary source of the MERS-CoV infecting humans, while bats may be the ultimate reservoir of the virus. Evidence includes the frequency with which the virus has been found in camels to which human cases have been exposed, seriological data which shows widespread transmission in camels, and the similarity of the camel CoV to the human CoV.[48]

On 6 June 2014, the Arab News newspaper highlighted the latest research findings in the New England Journal of Medicine in which a 44-year-old Saudi man who kept a herd of nine camels died of MERS in November 2013. His friends said they witnessed him applying a topical medicine to the nose of one of his ill camels—four of them reportedly sick with nasal discharge—seven days before he himself became stricken with MERS. Researchers sequenced the virus found in one of the sick camels and the virus that killed the man, and found that their genomes were identical. In that same article, the Arab News reported that as of 6 June 2014, there have been 689 cases of MERS reported within the Kingdom of Saudi Arabia with 283 deaths.[49]

Taxonomy

MERS-CoV is more closely related to the bat coronaviruses HKU4 and HKU5 (lineage 2C) than it is to SARS-CoV (lineage 2B) (2, 9), sharing more than 90% sequence identity with their closest relationships, bat coronaviruses HKU4 and HKU5 and therefore considered to belong to the same species by the International Committee on Taxonomy of Viruses (ICTV).

› Viruses
› ssRNA viruses
› Group: IV; positive-sense, single-stranded RNA viruses
› Order: Nidovirales
› Family: Coronaviridae
› Subfamily: Coronavirinae
› Genus: Betacoronavirus[51]
› Species: Betacoronavirus 1 (commonly called Human coronavirus OC43), Human coronavirus HKU1, Murine coronavirus, Pipistrellus bat coronavirus HKU5, Rousettus bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus, Tylonycteris bat coronavirus HKU4, MERS-CoV

Strains:

Microbiology

The virus grows readily on Vero cells and LLC-MK2 cells.[17]

The receptor for this virus is CD26 (dipeptidyl peptidase 4).[53]

Research and patent

Saudi officials had not given permission for Dr. Zaki, the first isolator of the human strain, to send a sample of the virus to Fouchier and were angered when Fouchier claimed the patent on the full genetic sequence of the Middle East respiratory syndrome coronavirus.[54]

The editor of The Economist observed, "Concern over security must not slow urgent work. Studying a deadly virus is risky. Not studying it is riskier."[54] Dr. Zaki was fired from his job at the hospital as a result of bypassing the Saudi ministry of health in his announcement and sharing his sample and findings.[55][56][57][58]

At their annual meeting of the World Health Assembly in May 2013, WHO chief Margaret Chan declared that intellectual property, or patents on strains of new virus, should not impede nations from protecting their citizens by limiting scientific investigations. Deputy Health Minister Ziad Memish raised concerns that scientists who held the patent for the MERS-CoV virus would not allow other scientists to use patented material and were therefore delaying the development of diagnostic tests.[59] Erasmus MC responded that the patent application did not restrict public health research into MERS coronavirus,[60] and that the virus and diagnostic tests were shipped—free of charge—to all that requested such reagents.

Mapping

There are a number of mapping efforts focused on tracking MERS coronavirus. On 2 May 2014, the Corona Map was launched to track the MERS coronavirus in realtime on the world map. The data is officially reported by WHO or the Ministry of Health of the respective country.[61] HealthMap also tracks case reports with inclusion of news and social media as data sources as part of HealthMap MERS. Lastly, South Korea was infected recently.

See also

References

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  2. ↑ "Disease Outbreak News". www.who.int. 8 Oct 2014.
  3. ↑ "Middle East respiratory syndrome coronavirus (MERS-CoV) – Republic of Korea". www.who.int. 24 May 2015.
  4. ↑ "Middle East Respiratory Syndrome (MERS) to the Far East: Hospital Associated Outbreak in South Korea - Re: Why the panic? South Korea's MERS response questioned". www.bmj.com/content/350/bmj.h3403/rr. 2 July 2015.
  5. ↑ Roos, Robert (16 Jun 2014). "Bangladesh has first MERS case". cidrap.umn.edu.
  6. ↑ "Florida MERS patient recovers". CNN.
  7. ↑ "Middle East respiratory syndrome coronavirus (MERS-CoV) – China". 31 May 2015.
  8. ↑ "Thailand confirms first Mers case: Health ministry". 18 June 2015.
  9. ↑ "Philippines Confirms First Case of MERS". TIME. 6 July 2015.
  10. ↑ "MERS Coronaviruses in Dromedary Camels, Egypt". June 2014. Retrieved 22 Apr 2014.
  11. 1 2 3 "ECDC Rapid Risk Assessment - Severe respiratory disease associated with a novel coronavirus" (PDF). 19 Feb 2013. Retrieved 22 Apr 2014.
  12. ↑ Saey, Tina Hesman (27 February 2013). "Scientists race to understand deadly new virus: SARS-like infection causes severe illness, but may not spread quickly". Science News. 183 (6). p. 5. doi:10.1002/scin.5591830603.
  13. ↑ Wernery U, Lau SK, Woo PC (2016) Genomics and zoonotic infections: Middle East respiratory syndrome. Rev Sci Tech 35(1):191-202. doi: 10.20506/rst.35.1.2427.
  14. ↑ Ali Mohamed Zaki; Sander van Boheemen; Theo M. Bestebroer; Albert D.M.E. Osterhaus; Ron A.M. Fouchier (8 November 2012). "Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia" (PDF). New England Journal of Medicine. 367 (19): 1814–20. doi:10.1056/NEJMoa1211721. PMID 23075143.
  15. 1 2 Falco, Miriam (24 September 2012). "New SARS-like virus poses medical mystery". CNN. Retrieved 27 September 2012.
  16. ↑ Dziadosz, Alexander (13 May 2013). "The doctor who discovered a new SARS-like virus says it will probably trigger an epidemic at some point, but not necessarily in its current form.". Reuters. Retrieved 25 May 2013.
  17. 1 2 3 4 "See Also". ProMED-mail. 2012-09-20. Retrieved 2013-05-31.
  18. ↑ "Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus - Vol. 19 No. 5 - May 2013 - CDC". Emerging Infectious Diseases. 2013-05-19. Retrieved 2013-06-01.
  19. ↑ Lau SK, Lee P, Tsang AK, Yip CC, Tse H, Lee RA, Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. J Virol. 2011;85:11325–37. DOIExtract
  20. ↑ 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 3573664Freely accessible. PMID 23422412.
  21. 1 2 3 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.
  22. ↑ Jia, HP; Look, DC; Shi, L; Hickey, M; Pewe, L; Netland, J; Farzan, M; Wohlford-Lenane, C; Perlman, S (December 2005). "ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia". Journal of Virology. 79 (23): 14614–14621. doi:10.1128/JVI.79.23.14614-14621.2005. PMC 1287568Freely accessible. PMID 16282461.
  23. ↑ Müller, MA.; Raj, VS.; Muth, D.; Meyer, B.; Kallies, S.; Smits, SL.; Wollny, R.; Bestebroer, TM.; Specht, S. (11 December 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. doi:10.1128/mBio.00515-12. PMC 3520110Freely accessible. PMID 23232719.
  24. 1 2 "Receptor for new coronavirus found". nature.com. 2013-03-13. Retrieved 2013-03-18.
  25. ↑ Cui, J.; Eden, J. S.; Holmes, E. C.; Wang, L. F. (2013). "Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): Implications for the origin and emergence of Middle East respiratory syndrome coronavirus". Virology Journal. 10: 304. doi:10.1186/1743-422X-10-304. PMC 3852826Freely accessible. PMID 24107353.
  26. ↑ WHO: Novel coronavirus infection – update (13 February 2013) (accessed 13 February 2013)
  27. ↑ "Fauci: New Virus Not Yet a 'threat to the world' (video)". Washington Times. 2012-08-31. Retrieved 2013-05-31.
  28. ↑ Knickmeyer, Ellen; Al Omran, Ahmed (20 Apr 2014). "Concerns Spread as New Saudi MERS Cases Spike". Retrieved 22 Apr 2014.
  29. ↑ "Centers for Disease Control and Prevention FAQ on MERS".
  30. ↑ DENISE GRADY (June 19, 2013). "Investigation Follows Trail of a Virus in Hospitals".
  31. ↑ Jonrl Aleccia (28 May 2014). "CDC Backtracks: Illinois Man Didn't Have MERS After All". Retrieved 2 June 2014.
  32. ↑ Corman VM, Ithete NL, Richards LR, Schoeman MC, Preiser W, Drosten C, Drexler JF (2014). "Rooting the phylogenetic tree of middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat". J Virol. 88 (19): 11297–11303. doi:10.1128/JVI.01498-14.
  33. ↑ Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH, Alhakeem R, Durosinloun A, Al Asmari M, Islam A, Kapoor A, Briese T, Daszak P, Al Rabeeah AA, Lipkin WI (2013). "Middle East respiratory syndrome coronavirus in bats, Saudi Arabia". Emerg Infect Dis. 19 (11): 1819–23. doi:10.3201/eid1911.131172. PMC 3837665Freely accessible. PMID 24206838.
  34. ↑ Wang Q, Qi J, Yuan Y, Xuan Y, Han P, Wan Y, Ji W, Li Y, Wu Y, Wang J, Iwamoto A, Woo PC, Yuen KY, Yan J, Lu G, Gao GF (2014). "Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26". Cell Host Microbe. 16 (3): 328–337. doi:10.1016/j.chom.2014.08.009.
  35. ↑ Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL, Ong SH, Al Rabeeah AA, Alhakeem RF, Assiri A, Al-Tawfiq JA, Albarrak A, Barry M, Shibl A, Alrabiah FA, Hajjar S, Balkhy HH, Flemban H, Rambaut A, Kellam P, Memish ZA (2014). "Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus". MBio. 5 (1): e01062–13. doi:10.1128/mBio.01062-13.
  36. 1 2 Doucleff, Michaeleen (28 September 2012). "Holy Bat Virus! Genome Hints At Origin Of SARS-Like Virus". NPR. Retrieved 29 September 2012.
  37. 1 2 Abedine, Saad (13 March 2013). "Death toll from new SARS-like virus climbs to 9". CNN. Retrieved 2013-03-13.
  38. ↑ Doucleff, Michaeleen (28 September 2012). "Holy Bat Virus! Genome Hints At Origin Of SARS-Like Virus". NPR. Retrieved 29 September 2012.
  39. ↑ jobs (2013-08-23). "Deadly coronavirus found in bats: Nature News & Comment". Nature.com. Retrieved 2014-01-19.
  40. 1 2 Augustina Annan; Heather J. Baldwin; Victor Max Corman (March 2013). "Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe". Emerging Infectious Disease journal - CDC. 19 (3). Retrieved 20 March 2013.
  41. ↑ Reusken, C. B. E. M.; Haagmans, B. L.; Müller, M. A.; Gutierrez, C.; Godeke, G. J.; Meyer, B.; Muth, D.; Raj, V. S.; Smits-De Vries, L.; Corman, V. M.; Drexler, J. F.; Smits, S. L.; El Tahir, Y. E.; De Sousa, R.; van Beek, J.; Nowotny, N.; van Maanen, K.; Hidalgo-Hermoso, E.; Bosch, B. J.; Rottier, P.; Osterhaus, A.; Gortázar-Schmidt, C.; Drosten, C.; Koopmans, M. P. G. (2013). "Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study". Lancet. Elsevier Ltd. doi:10.1016/S1473-3099.2813.2970164-6.
  42. 1 2 "Eurosurveillance - Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013". www.eurosurveillance.org. Retrieved 2015-09-14.
  43. ↑ Hemida, Maged G; Chu, Daniel KW; Poon, Ranawaka; Perera, Mohammad A A; Ng, Hoiyee-Y (Jul 2014). "MERS coronavirus in dromedary camel herd, Saudi Arabia.". Emerging Infectious Diseases. 20. doi:10.3201/eid2007.140571. The full-genome sequence of MERS-CoV from dromedaries in this study is 99.9% similar to genomes of human clade B MERS-CoV.
  44. ↑ Roos, Robert (17 Apr 2014). "MERS outbreaks grow; Malaysian case had camel link". Retrieved 22 Apr 2014.
  45. ↑ "Camels May Transmit New Middle Eastern Virus". 8 August 2013. Retrieved 8 August 2013.
  46. ↑ "Three camels hit by MERS coronavirus in Qatar". Qatar Supreme Council of Health. Retrieved 28 November 2013.
  47. ↑ Hemida, MG (2013). "Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013". Euro Surveillance. 18 (50).
  48. ↑ "Middle East respiratory syndrome coronavirus (MERS‐CoV)Summary and literature update – as of 27 March2014" (PDF). 27 Mar 2014. Retrieved 24 Apr 2014.
  49. ↑ Mohammed Rasooldeen, Fakeih: 80% drop in MERS infections, Arab News, Vol XXXIX, Number 183, Page 1, 6 June 2014.
  50. ↑ Roos, Robert (25 September 2013). UK agency picks name for new coronavirus isolate (Report). University of Minnesota, Minneapolis, MN: Center for Infectious Disease Research & Policy (CIDRAP).
  51. 1 2 Bermingham, A.; Chand, MA.; Brown, CS.; Aarons, E.; Tong, C.; Langrish, C.; Hoschler, K.; Brown, K.; Galiano, M. (27 September 2012). "Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012" (PDF). Euro Surveillance. 17 (40): 20290. PMID 23078800.
  52. ↑ "New Coronavirus Has Many Potential Hosts, Could Pass from Animals to Humans Repeatedly". ScienceDaily. Retrieved 13 December 2012.
  53. ↑ Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL (Mar 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. ScienceNews. 495 (7440): 251–4. doi:10.1038/nature12005. PMID 23486063. Lay summary – ScienceNews.
  54. 1 2 "Pandemic preparedness: Coming, ready or not". The Economist. 20 April 2013.
  55. ↑ "Egyptian Virologist Who Discovered New SARS-Like Virus Fears Its Spread". Mpelembe. 13 May 2013. Retrieved 25 May 2013.
  56. ↑ Ian Sample; Mark Smith (15 March 2013). "Coronavirus victim's widow tells of grief as scientists scramble for treatment". The Guardian. Retrieved 25 May 2013.
  57. ↑ Sample, Ian (15 March 2013). "Coronavirus: Is this the next pandemic?". The Guardian. Retrieved 25 May 2013.
  58. ↑ Yang, Jennifer (21 October 2012). "How medical sleuths stopped a deadly new SARS-like virus in its tracks". Toronto Star. Retrieved 25 May 2013.
  59. ↑ "WHO urges information sharing over novel coronavirus". BBC News. 23 May 2013.
  60. ↑ "Erasmus MC: no restrictions for public health research into MERS coronavirus" (Press release). Rotterdam: Erasmus MC. 24 May 2013.
  61. ↑ "Corona Map" (Press release). 2 May 2014.
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