Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoVancestors may be found in OldWorld bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.
Keywords: MERS-CoV, Saudi Arabia, spike protein, transmission, evolution, vaccine
References
- 1.World Health Organization WHO. Middle East respiratory syndrome coronavirus (MERS-CoV): Summary of Current Situation, Literature Update and Risk Assessment. 2015. [Google Scholar]
- 2.Cotten M, Watson SJ, Kellam P, Al-Rabeeah AA, Makhdoom HQ, Assiri A, Al-Tawfiq JA, Alhakeem RF, Madani H, Al Rabiah FA, Al Hajjar S, Al-nassir WN, Albarrak A, Flemban H, Balkhy HH, Alsubaie S, Palser AL, Gall A, Bashford-Rogers R, Rambaut A, Zumla AI, Memish ZA. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet. 2013;382(9909):1993–2002. doi: 10.1016/S0140-6736(13)61887-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.MBio. 2014.
- 4.Kim JY, Song JY, Yoon YK, Choi SH, Song YG, Kim SR, Son HJ, Jeong SY, Choi JH, Kim KM, Yoon HJ, Choi JY, Kim TH, Choi YH, Kim HB, Yoon JH, Lee J, Eom JS, Lee SO, Oh WS, Choi JH, Yoo JH, Kim WJ, Cheong HJ. Middle East respiratory syndrome infection control and prevention guideline for healthcare facilities. Infect Chemother. 2015;47(4):278–302. doi: 10.3947/ic.2015.47.4.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Mackay IM, Arden KE. MERS coronavirus: diagnostics, epidemiology and transmission. Virol J. 2015;12(1):222. doi: 10.1186/s12985-015-0439-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Zhang Z, Shen L, Gu X. Evolutionary dynamics of MERS-CoV: potential recombination, positive selection and transmission. Sci Rep. 2016;6:25049. doi: 10.1038/srep25049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814–1820. doi: 10.1056/NEJMoa1211721. [DOI] [PubMed] [Google Scholar]
- 8.Hijawi B, Abdallat M, Sayaydeh A, Alqasrawi S, Haddadin A, Jaarour N, Alsheikh S, Alsanouri T. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J. 2013;19(1):S12–S18. doi: 10.26719/2013.19.supp1.S12. [DOI] [PubMed] [Google Scholar]
- 9.World Health Organization WHO. Middle East respiratory syndrome coronavirus (MERS-CoV) 2016. [Google Scholar]
- 10.Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, Flemban H, Al-Nassir WN, Balkhy HH, Al-Hakeem RF, Makhdoom HQ, Zumla AI, Memish ZA. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752–761. doi: 10.1016/S1473-3099(13)70204-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;368(26):2487–2494. doi: 10.1056/NEJMoa1303729. [DOI] [PubMed] [Google Scholar]
- 12.Min CK, Cheon S, Ha NY, Sohn KM, Kim Y, Aigerim A, Shin HM, Choi JY, Inn KS, Kim JH, Moon JY, Choi MS, Cho NH, Kim YS. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep. 2016;6:25359. doi: 10.1038/srep25359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA, Al-Mugti H, Aloraini MS, Alkhaldi KZ, Almohammadi EL, Alraddadi BM, Gerber SI, Swerdlow DL, Watson JT, Madani TA. 2014 MERSCoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372(9):846–854. doi: 10.1056/NEJMoa1408636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Almekhlafi GA, Albarrak MM, Mandourah Y, Hassan S, Alwan A, Abudayah A, Altayyar S, Mustafa M, Aldaghestani T, Alghamedi A, Talag A, Malik MK, Omrani AS, Sakr Y. Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients. Crit Care. 2016;20(1):123. doi: 10.1186/s13054-016-1303-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Al-Hameed F, Wahla AS, Siddiqui S, Ghabashi A, Al-Shomrani M, Al-Thaqafi A, Tashkandi Y. Characteristics and outcomes of Middle East respiratory syndrome coronavirus patients admitted to an intensive care unit in Jeddah, Saudi Arabia. J Intensive Care Med. 2016;31(5):344–348. doi: 10.1177/0885066615579858. [DOI] [PubMed] [Google Scholar]
- 16.Balkhy HH, Perl TM, Arabi YM. Preventing healthcare-associated transmission of the Middle East respiratory syndrome (MERS): our Achilles heel. J Infect Public Health. 2016;9(3):208–212. doi: 10.1016/j.jiph.2016.04.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Brown C. Call for infection control to stem MERS. CMAJ. 2014;186(10):E349. doi: 10.1503/cmaj.109-4806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Hunter JC, Nguyen D, Aden B, Al Bandar Z, Al Dhaheri W, Abu Elkheir K, Khudair A, Al Mulla M, El Saleh F, Imambaccus H, Al Kaabi N, Sheikh FA, Sasse J, Turner A, Abdel Wareth L, Weber S A, Ameri A, Abu Amer W, Alami NN, Bunga S, Haynes LM, Hall AJ, Kallen AJ, Kuhar D, Pham H, Pringle K, Tong S, Whitaker BL, Gerber SI, Al Hosani FI. Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings, Abu Dhabi. Emerg Infect Dis. 2016;22(4):647–656. doi: 10.3201/eid2204.151615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Madani TA, Althaqafi AO, Alraddadi BM. Infection prevention and control guidelines for patients with Middle East Respiratory syndrome coronavirus (MERS-CoV) infection. Saudi Med J. 2014;35(8):897–913. [PubMed] [Google Scholar]
- 20.Zumla A, Hui DS. Infection control and MERS-CoV in health-care workers. Lancet. 2014;383(9932):1869–1871. doi: 10.1016/S0140-6736(14)60852-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Drexler JF, Corman VM, Drosten C. Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS. Antiviral Res. 2014;101:45–56. doi: 10.1016/j.antiviral.2013.10.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ, Fouchier RA. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio. 2012;3(6):e00473. doi: 10.1128/mBio.00473-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.de Groot RJ, Baker SC, Baric R, Enjuanes L, Gorbalenya AE, Holmes KV, Perlman S, Poon L, Rottier PJM, Talbot PJ, Woo PCY, Ziebuhr J. Family Coronaviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus taxonomy: classification and nomenclature of viruses. Ninth report of the International Committee on Taxonomy of Viruses. London, United Kingdom: Academic Press; 2012. pp. 806–820. [Google Scholar]
- 24.World Health Organization WHO. Middle East respiratory syndrome coronavirus (MERS-CoV). Fact sheet N°401. 2015. [Google Scholar]
- 25.De Benedictis P, Marciano S, Scaravelli D, Priori P, Zecchin B, Capua I, Monne I, Cattoli G. Alpha and lineage C betaCoV infections in Italian bats. Virus Genes. 2014;48(2):366–371. doi: 10.1007/s11262-013-1008-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L, Fouchier RA, Galiano M, Gorbalenya AE, Memish ZA, Perlman S, Poon LL, Snijder EJ, Stephens GM, Woo PC, Zaki AM, Zambon M, Ziebuhr J. Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol. 2013;87(14):7790–7792. doi: 10.1128/JVI.01244-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Reusken CB, Lina PH, Pielaat A, de Vries A, Dam-Deisz C, Adema J, Drexler JF, Drosten C, Kooi EA. Circulation of group 2 coronaviruses in a bat species common to urban areas in Western Europe. Vector Borne Zoonotic Dis. 2010;10(8):785–791. doi: 10.1089/vbz.2009.0173. [DOI] [PubMed] [Google Scholar]
- 28.Reusken CB, Raj VS, Koopmans MP, Haagmans BL. Cross host transmission in the emergence of MERS coronavirus. Curr Opin Virol. 2016;16:55–62. doi: 10.1016/j.coviro.2016.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Woo PC, Wang M, Lau SK, Xu H, Poon RW, Guo R, Wong BH, Gao K, Tsoi HW, Huang Y, Li KS, Lam CS, Chan KH, Zheng BJ, Yuen KY. Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features. J Virol. 2007;81(4):1574–1585. doi: 10.1128/JVI.02182-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Corman VM, Ithete NL, Richards LR, Schoeman MC, Preiser W, Drosten C, Drexler JF. Rooting the phylogenetic tree of Middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat. J Virol. 2014;88(19):11297–11303. doi: 10.1128/JVI.01498-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Ithete NL, Stoffberg S, Corman VM, Cottontail VM, Richards LR, Schoeman MC, Drosten C, Drexler JF, Preiser W. Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis. 2013;19(10):1697–1699. doi: 10.3201/eid1910.130946. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Rambaut A. MERS-coronavirus molecular epidemiology and genetic analysis —origin and evolution. 2014. [Google Scholar]
- 33.Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY, Gluecks I, Lattwein E, Bosch BJ, Drexler JF, Bornstein S, Drosten C, Müller MA. Antibodies against MERS coronavirus in dromedary camels, Kenya, 1992‒2013. Emerg Infect Dis. 2014;20(8):1319–1322. doi: 10.3201/eid2008.140596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Haagmans B A, Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R, Godeke GJ, Jonges M, Farag E, Diab A, Ghobashy H, Alhajri F, Al-Thani M, Al-Marri SA, Al Romaihi HE, Al Khal A, Bermingham A, Osterhaus A A, Hajri MM, Koopmans MP. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014;14(2):140–145. doi: 10.1016/S1473-3099(13)70690-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, Siu LY, Shehata MM, Kayed AS, Moatasim Y, Li M, Poon LL, Guan Y, Webby RJ, Ali MA, Peiris JS, Kayali G. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill. 2013;18(36):20574. doi: 10.2807/1560-7917.ES2013.18.36.20574. [DOI] [PubMed] [Google Scholar]
- 36.World Health Organization WHO. Latest updates on MERSCoV. 2016. [Google Scholar]
- 37.Graham RL, Baric RS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol. 2010;84(7):3134–3146. doi: 10.1128/JVI.01394-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Qian Z, Dominguez SR, Holmes KV. Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation. PLoS One. 2013;8(10):e76469. doi: 10.1371/journal.pone.0076469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.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. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251–254. doi: 10.1038/nature12005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, Guo D, Fu L, Cui Y, Liu X, Arledge KC, Chen YH, Zhang L, Wang X. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 2013;23(8):986–993. doi: 10.1038/cr.2013.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Yang Y, Liu C, Du L, Jiang S, Shi Z, Baric RS, Li F. Two mutations were critical for bat-to-human transmission of Middle East respiratory syndrome coronavirus. J Virol. 2015;89(17):9119–9123. doi: 10.1128/JVI.01279-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Modjarrad K. MERS-CoV vaccine candidates in development: The current landscape. Vaccine. 2016;34(26):2982–2987. doi: 10.1016/j.vaccine.2016.03.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Chu DK, Oladipo JO, Perera RA, Kuranga SA, Chan SM, Poon LL, Peiris M. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Nigeria, 2015. Euro Surveill. 2015;20(49):30086. doi: 10.2807/1560-7917.ES.2015.20.49.30086. [DOI] [PubMed] [Google Scholar]
- 44.Farag EA, Reusken CB, Haagmans BL, Mohran K S, Raj V, Pas SD, Voermans J, Smits SL, Godeke GJ, Al-Hajri MM, Alhajri FH, Al-Romaihi HE, Ghobashy H, El-Maghraby MM, El-Sayed A A, Thani MH, Al-Marri S, Koopmans MP. High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014. Infect Ecol Epidemiol. 2015;5(1):28305. doi: 10.3402/iee.v5.28305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Raj VS, Farag EA, Reusken CB, Lamers MM, Pas SD, Voermans J, Smits SL, Osterhaus AD, Al-Mawlawi N, Al-Romaihi H A, Hajri MM, El-Sayed AM, Mohran KA, Ghobashy H, Alhajri F, Al-Thani M, Al-Marri SA, El-Maghraby MM, Koopmans MP, Haagmans BL. Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014. Emerg Infect Dis. 2014;20(8):1339–1342. doi: 10.3201/eid2008.140663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S, Godeke GJ, Bestebroer TM, Zutt I M M, Bosch BJ, Rottier PJ, Osterhaus AD, Drosten C, Haagmans BL, Koopmans MP. Middle East respiratory syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. Euro Surveill. 2013;18(50):20662. doi: 10.2807/1560-7917.ES2013.18.50.20662. [DOI] [PubMed] [Google Scholar]
- 47.Reusken CB, Haagmans BL, Müller MA, Gutierrez C, Godeke GJ, Meyer B, Muth D, Raj V S-, De Vries L, Corman VM, Drexler JF, Smits SL, El Tahir YE, De Sousa R, van Beek J, Nowotny N, van Maanen K, Hidalgo-Hermoso E, Bosch BJ, Rottier P, Osterhaus A, Gortázar-Schmidt C, Drosten C, Koopmans MP. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis. 2013;13(10):859–866. doi: 10.1016/S1473-3099(13)70164-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Reusken CB, Farag EA, Jonges M, Godeke GJ, El-Sayed AM, Pas SD, Raj VS, Mohran KA, Moussa HA, Ghobashy H, Alhajri F, Ibrahim AK, Bosch BJ, Pasha SK, Al-Romaihi HE, Al-Thani M, Al-Marri SA, Al Hajri MM, Haagmans BL, Koopmans MP. Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014. Euro Surveill. 2014;19(23):20829. doi: 10.2807/1560-7917.ES2014.19.23.20829. [DOI] [PubMed] [Google Scholar]
- 49.Reusken CB, Schilp C, Raj VS, De Bruin E, Kohl RH, Farag EA, Haagmans BL, Al-Romaihi H, Le Grange F, Bosch BJ, Koopmans MP. MERS-CoV infection of alpaca in a region where MERS-CoV is endemic. Emerg Infect Dis. 2016;22(6):1129–1131. doi: 10.3201/eid2206.152113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Clin Microbiol Infect. 2015.
- 51.Memish ZA, Assiri A, Almasri M, Alhakeem RF, Turkestani A A, Rabeeah AA, Al-Tawfiq JA, Alzahrani A, Azhar E, Makhdoom HQ, Hajomar WH, Al-Shangiti AM, Yezli S. Prevalence of MERSCoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj. J Infect Dis. 2014;210(7):1067–1072. doi: 10.1093/infdis/jiu150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Gautret P, Charrel R, Benkouiten S, Belhouchat K, Nougairede A, Drali T, Salez N, Memish Z A, Masri M, Lagier JC, Million M, Raoult D, Brouqui P, Parola P. Lack of MERS coronavirus but prevalence of influenza virus in French pilgrims after 2013 Hajj. Emerg Infect Dis. 2014;20(4):728–730. doi: 10.3201/eid2004.131708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Barasheed O, Rashid H, Alfelali M, Tashani M, Azeem M, Bokhary H, Kalantan N, Samkari J, Heron L, Kok J, Taylor J, El Bashir H, Memish ZA, Haworth E, Holmes EC, Dwyer DE, Asghar A, Booy R. Hajj Research Team. Viral respiratory infections among Hajj pilgrims in 2013. Virol Sin. 2014;29(6):364–371. doi: 10.1007/s12250-014-3507-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Alraddadi BM, Watson JT, Almarashi A, Abedi GR, Turkistani A, Sadran M, Housa A, Almazroa MA, Alraihan N, Banjar A, Albalawi E, Alhindi H, Choudhry AJ, Meiman JG, Paczkowski M, Curns A, Mounts A, Feikin DR, Marano N, Swerdlow DL, Gerber SI, Hajjeh R, Madani TA. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22(1):49–55. doi: 10.3201/eid2201.151340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Reusken CB, Farag EA, Haagmans BL, Mohran KA, Godeke G 5, Raj S, Alhajri F, Al-Marri SA, Al-Romaihi HE, Al-Thani M, Bosch BJ, van der Eijk AA, El-Sayed AM, Ibrahim AK, Al-Molawi N M M, Pasha SK, Drosten C, Al Hajri MM, Koopmans MP. Occupational exposure to dromedaries and risk for MERS-CoV infection, Qatar, 2013–2014. Emerg Infect Dis. 2015;21(8):1422–1425. doi: 10.3201/eid2108.150481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Memish ZA, Cotten M, Meyer B, Watson SJ, Alsahafi AJ, Al Rabeeah AA, Corman VM, Sieberg A, Makhdoom HQ, Assiri A A, Masri M, Aldabbagh S, Bosch BJ, Beer M, Müller MA, Kellam P, Drosten C. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. 2014;20(6):1012–1015. doi: 10.3201/eid2006.140402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM, Madani TA. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014;370(26):2499–2505. doi: 10.1056/NEJMoa1401505. [DOI] [PubMed] [Google Scholar]
- 58.World Health Organization WHO. Laboratory testing for Middle East respiratory syndrome coronavirus: interim guidance. 2015. [Google Scholar]
- 59.Corman VM, Müller MA, Costabel U, Timm J, Binger T, Meyer B, Kreher P, Lattwein E, Eschbach-Bludau M, Nitsche A, Bleicker T, Landt O, Schweiger B, Drexler JF, Osterhaus AD, Haagmans BL, Dittmer U, Bonin F, Wolff T, Drosten C. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill. 2012;17(49):1. doi: 10.2807/ese.17.49.20334-en. [DOI] [PubMed] [Google Scholar]
- 60.Muth D, Corman VM, Meyer B, Assiri A, Al-Masri M, Farah M, Steinhagen K, Lattwein E, Al-Tawfiq JA, Albarrak A, Müller MA, Drosten C, Memish ZA. Infectious Middle East respiratory syndrome coronavirus excretion and serotype variability based on live virus isolates from patients in Saudi Arabia. J Clin Microbiol. 2015;53(9):2951–2955. doi: 10.1128/JCM.01368-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Meyer B, Drosten C, Müller MA. Serological assays for emerging coronaviruses: challenges and pitfalls. Virus Res. 2014;194:175–183. doi: 10.1016/j.virusres.2014.03.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Reusken CB, Messadi L, Feyisa A, Ularamu H, Godeke GJ, Danmarwa A, Dawo F, Jemli M, Melaku S, Shamaki D, Woma Y, Wungak Y, Gebremedhin EZ, Zutt I, Bosch BJ, Haagmans BL, Koopmans MP. Geographic distribution of MERS coronavirus among dromedary camels, Africa. Emerg Infect Dis. 2014;20(8):1370–1374. doi: 10.3201/eid2008.140590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.Liljander A, Meyer B, Jores J, Müller MA, Lattwein E, Njeru I, Bett B, Drosten C, Corman VM. MERS-CoV antibodies in humans, Africa, 2013–2014. Emerg Infect Dis. 2016;22(6):1086–1089. doi: 10.3201/eid2206.160064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, Sieberg A, Aldabbagh S, Bosch BJ, Lattwein E, Alhakeem RF, Assiri AM, Albarrak AM, Al-Shangiti AM, Al-Tawfiq JA, Wikramaratna P, Alrabeeah AA, Drosten C, Memish ZA. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect Dis. 2015;15(5):559–564. doi: 10.1016/S1473-3099(15)70090-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65.Butt TS, Koutlakis-Barron I, Al Jumaah S, Al Thawadi S, Al Mofada S. Infection control and prevention practices implemented to reduce transmission risk of Middle East respiratory syndrome-coronavirus in a tertiary care institution in Saudi Arabia. Am J Infect Control. 2016;44(5):605–611. doi: 10.1016/j.ajic.2016.01.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 66.Hastings DL, Tokars JI, Abdel Aziz IZ, Alkhaldi KZ, Bensadek AT, Alraddadi BM, Jokhdar H, Jernigan JA, Garout MA, Tomczyk SM, Oboho IK, Geller AI, Arinaminpathy N, Swerdlow DL, Madani TA. Outbreak of Middle East respiratory syndrome at tertiary care hospital, Jeddah, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22(5):794–801. doi: 10.3201/eid2205.151797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Nishiura H, Endo A, Saitoh M, Kinoshita R, Ueno R, Nakaoka S, Miyamatsu Y, Dong Y, Chowell G, Mizumoto K. Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis. BMJ Open. 2016;6(2):e009936. doi: 10.1136/bmjopen-2015-009936. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68.Bermingham A, Chand MA, Brown CS, Aarons E, Tong C, Langrish C, Hoschler K, Brown K, Galiano M, Myers R, Pebody RG, Green HK, Boddington NL, Gopal R, Price N, Newsholme W, Drosten C, Fouchier RA, Zambon M. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill. 2012;17(40):20290. [PubMed] [Google Scholar]
- 69.Breakwell L, Pringle K, Chea N, Allen D, Allen S, Richards S, Pantones P, Sandoval M, Liu L, Vernon M, Conover C, Chugh R, De Maria A, Burns R, Smole S, Gerber SI, Cohen NJ, Kuhar D, Haynes LM, Schneider E, Kumar A, Kapoor M, Madrigal M, Swerdlow DL, Feikin DR. Lack of transmission among close contacts of patient with case of middle east respiratory syndrome imported into the United States, 2014. Emerg Infect Dis. 2015;21(7):1128–1134. doi: 10.3201/eid2107.150054. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.Kraaij-Dirkzwager M, Timen A, Dirksen K, Gelinck L, Leyten E, Groeneveld P, Jansen C, Jonges M, Raj S, Thurkow I v, Gageldonk-Lafeber R, van der Eijk A, Koopmans M. MERS-CoV Outbreak Investigation Team of the Netherlands. Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014. Euro Surveill. 2014;19(21):20817. doi: 10.2807/1560-7917.ES2014.19.21.20817. [DOI] [PubMed] [Google Scholar]
- 71.Wiboonchutikul S, Manosuthi W, Likanonsakul S, Sangsajja C, Kongsanan P, Nitiyanontakij R, Thientong V, Lerdsamran H, Puthavathana P. Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand. Antimicrob Resist Infect Control. 2016;5(1):21. doi: 10.1186/s13756-016-0120-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72.Wang Y, Liu D, Shi W, Lu R, Wang W, Zhao Y, Deng Y, Zhou W, Ren H, Wu J, Wang Y, Wu G, Gao GF, Tan W. Origin and possible genetic recombination of the Middle East respiratory syndrome coronavirus from the first imported case in China: phylogenetics and coalescence analysis. MBio. 2015;6(5):e01280. doi: 10.1128/mBio.01280-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73.Assiri AM, Midgley CM, Abedi GR, Saeed AB, Almasri MM, Lu X, Al-Abdely HM, Abdalla O, Mohammed M, Algarni HS, Alhakeem RF, Sakthivel SK, Nooh R, Alshayab Z, Alessa M, Srinivasamoorthy G, Al Qahtani SY, Kheyami A, Haj Omar WH, Banaser TM, Esmaeel A, Hall AJ, Curns AT, Tamin A, Alsharef AA, Erdman D, Watson JT, Gerber SI. Epidemiology of a novel recombinant MERS-CoV in humans in Saudi Arabia. J Infect Dis. 2016;214(5):712–721. doi: 10.1093/infdis/jiw236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 74.Wernery U, Lau SK, Woo PC. Genomics and zoonotic infections: Middle East respiratory syndrome. Rev Sci Tech. 2016;35(1):191–202. doi: 10.20506/rst.35.1.2427. [DOI] [PubMed] [Google Scholar]
- 75.Chu DK, Poon LL, Gomaa MM, Shehata MM, Perera RA, Abu Zeid D, El Rifay AS, Siu LY, Guan Y, Webby RJ, Ali MA, Peiris M, Kayali G. MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis. 2014;20(6):1049–1053. doi: 10.3201/eid2006.140299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 76.Smits SL, Raj VS, Pas SD, Reusken CB, Mohran K, Farag EA, Al-Romaihi H A, Hajri MM, Haagmans BL, Koopmans MP. Reliable typing of MERS-CoV variants with a small genome fragment. J Clin Virol. 2015;64:83–87. doi: 10.1016/j.jcv.2014.12.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 77.Kandeil A, Shehata MM, El Shesheny R, Gomaa MR, Ali MA, Kayali G. Complete genome sequence of Middle East respiratory syndrome coronavirus isolated from a dromedary camel in Egypt. Genome Announc. 2016;4(2):e00309. doi: 10.1128/genomeA.00309-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 78.Dudas G, Rambaut A. MERS-CoV recombination: implications about the reservoir and potential for adaptation. 2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 79.McRoy WC, Baric RS. Amino acid substitutions in the S2 subunit of mouse hepatitis virus variant V51 encode determinants of host range expansion. J Virol. 2008;82(3):1414–1424. doi: 10.1128/JVI.01674-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80.Sheahan T, Rockx B, Donaldson E, Sims A, Pickles R, Corti D, Baric R. Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium. J Virol. 2008;82(5):2274–2285. doi: 10.1128/JVI.02041-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81.Durai P, Batool M, Shah M, Choi S. Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control. Exp Mol Med. 2015;47(8):e181. doi: 10.1038/emm.2015.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Kim Y, Cheon S, Min CK, Sohn KM, Kang YJ, Cha YJ, Kang JI, Han SK, Ha NY, Kim G, Aigerim A, Shin HM, Choi MS, Kim S, Cho HS, Kim YS, Cho NH. Spread of mutant Middle East respiratory syndrome coronavirus with reduced affinity to human CD26 during the South Korean outbreak. MBio. 2016;7(2):e00019. doi: 10.1128/mBio.00019-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 83.Forni D, Filippi G, Cagliani R, De Gioia L, Pozzoli U, Al-Daghri N, Clerici M, Sironi M. The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses. Sci Rep. 2015;5:14480. doi: 10.1038/srep14480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 84.Ho BL, Cheng SC, Shi L, Wang TY, Ho KI, Chou CY. Critical Assessment of the important residues involved in the dimerization and catalysis of MERS coronavirus main protease. PLoS One. 2015;10(12):e0144865. doi: 10.1371/journal.pone.0144865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85.Omrani AS, Saad MM, Baig K, Bahloul A, Abdul-Matin M, Alaidaroos AY, Almakhlafi GA, Albarrak MM, Memish ZA, Albarrak AM. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14(11):1090–1095. doi: 10.1016/S1473-3099(14)70920-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86.Spanakis N, Tsiodras S, Haagmans BL, Raj VS, Pontikis K, Koutsoukou A, Koulouris NG, Osterhaus AD, Koopmans MP, Tsakris A. Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen. Int J Antimicrob Agents. 2014;44(6):528–532. doi: 10.1016/j.ijantimicag.2014.07.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 87.Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H. Treatment with interferon-α2b and ribavirin improves outcome in MERSCoV-infected rhesus macaques. Nat Med. 2013;19(10):1313–1317. doi: 10.1038/nm.3362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 88.Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, Johnson RF, Olinger G J, Frieman MB, Holbrook MR, Jahrling PB, Hensley L. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J Gen Virol. 2014;95(3):571–577. doi: 10.1099/vir.0.061911-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 89.Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016;9(3):227–230. doi: 10.1016/j.jiph.2016.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 90.Lu L, Liu Q, Zhu Y, Chan KH, Qin L, Li Y, Wang Q, Chan JF, Du L, Yu F, Ma C, Ye S, Yuen KY, Zhang R, Jiang S. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat Commun. 2014;5:3067. doi: 10.1038/ncomms4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 91.Bosch BJ, Martina BE, Van Der Zee R, Lepault J, Haijema BJ, Versluis C, Heck AJ, De Groot R, Osterhaus AD, Rottier PJ. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci USA. 2004;101(22):8455–8460. doi: 10.1073/pnas.0400576101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 92.Liu S, Xiao G, Chen Y, He Y, Niu J, Escalante CR, Xiong H, Farmar J, Debnath AK, Tien P, Jiang S. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet. 2004;363(9413):938–947. doi: 10.1016/S0140-6736(04)15788-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 93.Channappanavar R, Lu L, Xia S, Du L, Meyerholz DK, Perlman S, Jiang S. Protective effect of intranasal regimens containing peptidic Middle East respiratory syndrome coronavirus fusion inhibitor against MERS-CoV infection. J Infect Dis. 2015;212(12):1894–1903. doi: 10.1093/infdis/jiv325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 94.Lei J, Mesters JR, Drosten C, Anemüller S, Ma Q, Hilgenfeld R. Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features. Antiviral Res. 2014;109:72–82. doi: 10.1016/j.antiviral.2014.06.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 95.Corman VM, Albarrak AM, Omrani AS, Albarrak MM, Farah ME, Almasri M, Muth D, Sieberg A, Meyer B, Assiri AM, Binger T S L, Al-Tawfiq J, Müller MA, Drosten C, Memish ZA. Viral shedding and antibody response in 37 patients with MERS-coronavirus infection. Clin Infect Dis. 2015;62(4):477–483. doi: 10.1093/cid/civ951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 96.Muth D, Corman VM, Meyer B, Assiri A, Al-Masri M, Farah M, Steinhagen K, Lattwein E, Al-Tawfiq JA, Albarrak A, Müller MA, Drosten C, Memish ZA. Infectious Middle East respiratory syndrome coronavirus excretion and serotype variability based on live virus isolates from patients in Saudi Arabia. J Clin Microbiol. 2015;53(9):2951–2955. doi: 10.1128/JCM.01368-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 97.Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, Chen Y, Yu F, Tseng CT, Zhou Y, Jiang S. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PLoS One. 2013;8(12):e81587. doi: 10.1371/journal.pone.0081587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 98.Kumar V, Jung YS, Liang PH. Anti-SARS coronavirus agents: a patent review (2008‒present) Expert Opin Ther Pat. 2013;23(10):1337–1348. doi: 10.1517/13543776.2013.823159. [DOI] [PubMed] [Google Scholar]
- 99.Ma C, Li Y, Wang L, Zhao G, Tao X, Tseng CT, Zhou Y, Du L, Jiang S. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines. Vaccine. 2014;32(18):2100–2108. doi: 10.1016/j.vaccine.2014.02.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 100.Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, Lees CR, Zhou T, Yassine HM, Kanekiyo M, Yang ZY, Chen X, Becker MM, Freeman M, Vogel L, Johnson JC, Olinger G, Todd JP, Bagci U, Solomon J, Mollura DJ, Hensley L, Jahrling P, Denison MR, Rao SS, Subbarao K, Kwong PD, Mascola JR, Kong WP, Graham BS. Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun. 2015;6:7712. doi: 10.1038/ncomms8712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101.Zhang N, Tang J, Lu L, Jiang S, Du L. Receptor-binding domainbased subunit vaccines against MERS-CoV. Virus Res. 2015;202:151–159. doi: 10.1016/j.virusres.2014.11.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 102.Lan J, Yao Y, Deng Y, Chen H, Lu G, Wang W, Bao L, Deng W, Wei Q, Gao GF, Qin C, Tan W. Recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against Middle East respiratory syndrome coronavirus challenge. EBioMedicine. 2015;2(10):1438–1446. doi: 10.1016/j.ebiom.2015.08.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 103.Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Glenn GM, Smith GE, Frieman MB. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014;32(26):3169–3174. doi: 10.1016/j.vaccine.2014.04.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 104.Song F, Fux R, Provacia LB, Volz A, Eickmann M, Becker S, Osterhaus AD, Haagmans BL, Sutter G. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol. 2013;87(21):11950–11954. doi: 10.1128/JVI.01672-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 105.Volz A, Kupke A, Song F, Jany S, Fux R, Shams-Eldin H, Schmidt J, Becker C, Eickmann M, Becker S, Sutter G. Protective efficacy of recombinant modified vaccinia virus Ankara delivering Middle East respiratory syndrome coronavirus spike glycoprotein. J Virol. 2015;89(16):8651–8656. doi: 10.1128/JVI.00614-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 106.Guo X, Deng Y, Chen H, Lan J, Wang W, Zou X, Hung T, Lu Z, Tan W. Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vectorbased vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus. Immunology. 2015;145(4):476–484. doi: 10.1111/imm.12462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 107.Kim E, Okada K, Kenniston T, Raj VS, Al Hajri MM, Farag E A, Hajri F, Osterhaus AD, Haagmans BL, Gambotto A. Immunogenicity of an adenoviral-based Middle East respiratory syndrome coronavirus vaccine in BALB/c mice. Vaccine. 2014;32(45):5975–5982. doi: 10.1016/j.vaccine.2014.08.058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 108.novio. GLS-5300 SynCon® immunotherapy targeting Middle East Respiratory Syndrome. 2016. Available from http://www.inovio.com/products/infectious-disease-vaccines/mers/ (Accessed June 20, 2016)
- 109.Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F L, Casse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med. 2015;7(301):301. doi: 10.1126/scitranslmed.aac7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 110.Corti D, Zhao J, Pedotti M, Simonelli L, Agnihothram S, Fett C, Fernandez-Rodriguez B, Foglierini M, Agatic G, Vanzetta F, Gopal R, Langrish CJ, Barrett NA, Sallusto F, Baric RS, Varani L, Zambon M, Perlman S, Lanzavecchia A. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. Proc Natl Acad Sci USA. 2015;112(33):10473–10478. doi: 10.1073/pnas.1510199112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 111.Jiang L, Wang N, Zuo T, Shi X, Poon KM, Wu Y, Gao F, Li D, Wang R, Guo J, Fu L, Yuen KY, Zheng BJ, Wang X, Zhang L. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci Transl Med. 2014;6(234):234. doi: 10.1126/scitranslmed.3008140. [DOI] [PubMed] [Google Scholar]
- 112.Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT, Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA. 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. 2015;112(28):8738–8743. doi: 10.1073/pnas.1510830112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 113.Ying T, Du L, Ju TW, Prabakaran P, Lau CC, Lu L, Liu Q, Wang L, Feng Y, Wang Y, Zheng BJ, Yuen KY, Jiang S, Dimitrov DS. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J Virol. 2014;88(14):7796–7805. doi: 10.1128/JVI.00912-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 114.Ying T, Prabakaran P, Du L, Shi W, Feng Y, Wang Y, Wang L, Li W, Jiang S, Dimitrov DS, Zhou T. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat Commun. 2015;6:8223. doi: 10.1038/ncomms9223. [DOI] [PMC free article] [PubMed] [Google Scholar]