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. 2016 Dec 23;10(4):377–382. doi: 10.1007/s11684-016-0466-7

From SARS to MERS: evidence and speculation

Hainv Gao 1,2, Hangping Yao 1,2, Shigui Yang 1,2, Lanjuan Li 1,2,
PMCID: PMC7088694  PMID: 27726088

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic pathogen. In 2012, the infectious outbreak caused by MERS-CoV in Saudi Arabia has spread to more than 1600 patients in 26 countries, resulting in over 600 deaths.Without a travel history, few clinical and radiological features can reliably differentiate MERS from SARS. But in real world, comparing with SARS, MERS presents more vaguely defined epidemiology, more severe symptoms, and higher case fatality rate. In this review, we summarize the recent findings in the field of MERS-CoV, especially its molecular virology, interspecies mechanisms, clinical features, antiviral therapies, and the further investigation into this disease. As a newly emerging virus, many questions are not fully answered, including the exact mode of transmission chain, geographical distribution, and animal origins. Furthermore, a new protocol needs to be launched to rapidly evaluate the effects of unproven antiviral drugs and vaccine to fasten the clinical application of new drugs.

Keywords: middle east respiratory syndrome, animal origin, cross-species transmission, monoclonal antibody

References

  • 1.World Health Organization. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003[EB/OL]. 2004–04–21.http://www.who.int/csr/sars/country/table2004_04_21/en/ (Acessed July 27, 2015)
  • 2.World Health Organization. Middel East respiratory syndrome coronavirus (MERS-CoV) Saudi Arabia. http://www.who.int/csr/ don/23-march-2016-mers-saudi-arabia/en/(Acessed August 6, 2016)
  • 3.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]
  • 4.World Health Organization. Background and summary of novel coronavirus infection—as of 22 November 2013. 2013. http://www.who.int/ csr/disease/coronavirus_infections/Update12_ MERSCoV_update_22Nov13. Pdf (Acessed August 6, 2016)
  • 5.World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV)—Republic of Korea. Geneva: WHO. 24 May 2015. http://www.who.int/csr/don/14-july-2015-mers-korea/ en/ (Accessed July 15 2015)
  • 6.Zumla A H D, Perlman S. Middle East respiratory syndrome. Lancet. 2015;386(9997):995–1007. doi: 10.1016/S0140-6736(15)60454-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Lau SK, Li KS, Tsang AK, Lam CS, Ahmed S, Chen H, Chan KH, Woo PC, Yuen KY. Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. J Virol. 2013;87(15):8638–8650. doi: 10.1128/JVI.01055-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23. doi: 10.1007/978-1-4939-2438-7_1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.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]
  • 10.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;5:28305. doi: 10.3402/iee.v5.28305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Chan SM, Damdinjav B, Perera RA, Chu DK, Khishgee B, Enkhbold B, Poon LL, Peiris M. Absence of MERS-Coronavirus in Bactrian Camels, Southern Mongolia, November 2014. Emerg Infect Dis. 2015;21(7):1269–1271. doi: 10.3201/eid2107.150178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Briese T, Mishra N, Jain K, Zalmout IS, Jabado OJ, Karesh WB, Daszak P, Mohammed OB, Alagaili AN, Lipkin WI. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia. MBio. 2014;5(3):e01146–e14. doi: 10.1128/mBio.01146-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Haagmans BL, van den Brand JM, Provacia LB, Raj VS, Stittelaar KJ, Getu S, de Waal L, Bestebroer TM, van Amerongen G, Verjans GM, Fouchier RA, Smits SL, Kuiken T, Osterhaus AD. Asymptomatic Middle East respiratory syndrome coronavirus infection in rabbits. J Virol. 2015;89(11):6131–6135. doi: 10.1128/JVI.00661-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.van Doremalen N, Miazgowicz KL, Milne-Price S, Bushmaker T, Robertson S, Scott D, Kinne J, McLellan JS, Zhu J, Munster VJ. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol. 2014;88(16):9220–9232. doi: 10.1128/JVI.00676-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Barlan A, Zhao J, Sarkar MK, Li K M, Cray P J, Perlman S, Gallagher T. Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection. J Virol. 2014;88(9):4953–4961. doi: 10.1128/JVI.00161-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M, Nkrumah EE, Badu EK, Anti P, Agbenyega O, Meyer B, Oppong S, Sarkodie YA, Kalko EK, Lina PH, Godlevska EV, Reusken C, Seebens A, Gloza-Rausch F, Vallo P, Tschapka M, Drosten C, Drexler JF. Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerg Infect Dis. 2013;19(3):456–459. doi: 10.3201/eid1903.121503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Yang Y, Du L, Liu C, Wang L, Ma C, Tang J, Baric RS, Jiang S, Li F. Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus. Proc Natl Acad Sci USA. 2014;111(34):12516–12521. doi: 10.1073/pnas.1405889111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH, Alhakeem R, Durosinloun A A, Asmari M, Islam A, Kapoor A, Briese T, Daszak P A, Rabeeah AA, Lipkin WI. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis. 2013;19(11):1819–1823. doi: 10.3201/eid1911.131172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Raj VS, Mou H, Smits SL, Dekkers D M M, 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]
  • 20.Meyerholz DK, Lambertz AM, McCray PB. Dipeptidyl peptidase 4 distribution in the human respiratory tract: implications for the middle east respiratory syndrome. Am J Pathol. 2015;186(1):78–86. doi: 10.1016/j.ajpath.2015.09.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Siu KL, Yeung ML, Kok KH, Yuen KS, Kew C, Lui PY, Chan CP, Tse H, Woo PC, Yuen KY, Jin DY. Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response. J Virol. 2014;88(9):4866–4876. doi: 10.1128/JVI.03649-13. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 22.Faure E, Poissy J, Goffard A, Fournier C, Kipnis E, Titecat M, Bortolotti P, Martinez L, Dubucquoi S, Dessein R, Gosset P, Mathieu D, Guery B. Distinct immune response in two MERS-CoVinfected patients: can we go from bench to bedside? PLoS ONE 2014; 9(2): e88716 [DOI] [PMC free article] [PubMed]
  • 23.Josset L, Menachery VD, Gralinski LE, Agnihothram S, Sova P, Carter VS, Yount BL, Graham RL, Baric RS, Katze MG. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. MBio. 2013;4(3):e00165–e13. doi: 10.1128/mBio.00165-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, Flemban H, Al-Nassir WN, Balkhy H A-, 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]
  • 25.Eckerle I M M, Kallies S, Gotthardt DN, Drosten C. In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East respiratory syndrome (MERS) coronavirus infection. Virol J. 2013;23(10):359. doi: 10.1186/1743-422X-10-359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, Selim MA, Al Mutairi M, Al Nakhli D, Al Aidaroos AY, Al Sherbeeni N, Al-Khashan HI, Memish ZA, Albarrak AM. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301–306. doi: 10.1016/j.ijid.2014.09.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Memish ZA, Al-Tawfiq JA, Makhdoom HQ, Al-Rabeeah AA, Assiri A, Alhakeem RF, AlRabiah FA, Al Hajjar S, Albarrak A, Flemban H, Balkhy H, Barry M, Alhassan S, Alsubaie S, Zumla A. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study. Clin Microbiol Infect. 2014;20(5):469–474. doi: 10.1111/1469-0691.12562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Al-Abdallat MM, Payne DC, Alqasrawi S, Rha B, Tohme RA, Abedi G A, Nsour M, Iblan I, Jarour N, Farag NH, Haddadin A, Al-Sanouri T, Tamin A, Harcourt JL, Kuhar DT, Swerdlow DL, Erdman DD, Pallansch MA, Haynes LM, Gerber SI, Sabri N, Al Azhari M, Khazali H, Al Maayah M, Bilbeisi A, Dawood N, Al Zubi B, Meflih J, Mounds T, Fitzner J, Eltom A, Mafi A, Miao C, Caidi H, Trivedi S, Kamili S, Hall AJ, Curns A, Moore J, Pham H, Zimmerman C, Farnon E, Giorgi G, Gerber R. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59(9):1225–1233. doi: 10.1093/cid/ciu359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Assiri A, McGeer A, Perl TM, Price C A, Rabeeah AA, Cummings DA, Alabdullatif ZN, Assad M, Almulhim A, Makhdoom H, Madani H, Alhakeem R, Al-Tawfiq JA, Cotten M, Watson SJ, Kellam P, Zumla A M Z K M-C I Team. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369(5):407–416. doi: 10.1056/NEJMoa1306742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Al-Tawfiq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, Ujayli A, Memish ZA. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis. 2014;59(2):160–165. doi: 10.1093/cid/ciu226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, Hawa H, Alothman A, Khaldi A, Al Raiy B. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160(6):389–397. doi: 10.7326/M13-2486. [DOI] [PubMed] [Google Scholar]
  • 32.Thabet F, Chehab M, Bafaqih H, Al Mohaimeed S. Middle East respiratory syndrome coronavirus in children. Saudi Med J. 2015;36(4):484–486. doi: 10.15537/smj.2015.4.10243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Denison MR. Severe acute respiratory syndrome coronavirus pathogenesis, disease and vaccines: an update. Pediatr Infect Dis J. 2004;23:S207–S214. doi: 10.1097/01.inf.0000144666.95284.05. [DOI] [PubMed] [Google Scholar]
  • 34.Bin Seo Y, Heo JY, Song MS, Lee J, Kim EH, Park SJ, Kwon HI, Kim SM, Kim YI, Si YJ, Lee IW, Baek YH, Choi WS, Min J, Jeong HW, Choi YK. Environmental contamination and viral shedding in MERS patients during MERS-CoV Outbreak in South Korea. Clin Infect Dis. 2016;62(6):755–760. doi: 10.1093/cid/civ1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Hui DS, Memish ZA, Zumla A. Severe acute respiratory syndrome vs. the Middle East respiratory syndrome. Curr Opin Pulm Med. 2014;20(3):233–241. doi: 10.1097/MCP.0000000000000046. [DOI] [PubMed] [Google Scholar]
  • 36.de Wilde AH, Raj VS, Oudshoorn D, Bestebroer TM, van Nieuwkoop S, Limpens RW, Posthuma CC, van der Meer Y, Bárcena M, Haagmans BL, Snijder EJ, van den Hoogen BG. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-a treatment. J Gen Virol. 2013;94:1749–1760. doi: 10.1099/vir.0.052910-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep. 2013;3:1686. doi: 10.1038/srep01686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Omrani AS, Saad MM, Baig K, Bahloul A, Abdul-Matin M, Alaidaroos AY, Almakhlafi GA, Albarrak MM, Memish ZA, Albarrak AM. Ribavirin and interferon α-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]
  • 39.Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect. 2013;67(6):606–616. doi: 10.1016/j.jinf.2013.09.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Sui J, Li W, Murakami A, Tamin A M L, Wong SK, Moore MJ, Tallarico AS, Olurinde M, Choe H, Anderson LJ, Bellini WJ, Farzan M, Marasco WA. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. 2004;101(8):2536–2541. doi: 10.1073/pnas.0307140101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.ter Meulen J, Bakker AB, van den Brink EN, Weverling GJ, Martina BE, Haagmans BL, Kuiken T, de Kruif J, Preiser W, Spaan W, Gelderblom HR, Goudsmit J, Osterhaus AD. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet. 2004;363(9427):2139–2141. doi: 10.1016/S0140-6736(04)16506-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, Murphy BR, Rappuoli R, Lanzavecchia A. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 2004;10(8):871–875. doi: 10.1038/nm1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Du L, Zhao G, Yang Y, Qiu H, Wang L, Kou Z, Tao X, Yu H, Sun S, Tseng CT, Jiang S, Li F, Zhou Y. A conformation-dependent neutralizing monoclonal antibody specifically targeting receptorbinding domain in Middle East respiratory syndrome coronavirus spike protein. J Virol. 2014;88(12):7045–7053. doi: 10.1128/JVI.00433-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.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]
  • 45.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):234ra59. doi: 10.1126/scitranslmed.3008140. [DOI] [PubMed] [Google Scholar]
  • 46.Tang XC, Agnihothram SS, Jiao Y, Stanhope J, Graham RL, Peterson EC, Avnir Y, Tallarico AS, Sheehan J, Zhu Q, Baric RS, Marasco WA. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc Natl Acad Sci USA. 2014;111(19):E2018–E2026. doi: 10.1073/pnas.1402074111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Ying T, Li H, Lu L, Dimitrov DS, Jiang S. Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes Infect. 2015;17(2):142–148. doi: 10.1016/j.micinf.2014.11.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.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]
  • 49.Borio L, Cox E, Lurie N. Combating emerging threats—accelerating the availability of medical therapies. N Engl J Med. 2015;373(11):993–995. doi: 10.1056/NEJMp1508708. [DOI] [PubMed] [Google Scholar]
  • 50.Haagmans BL, van den Brand JM, Raj VS, Volz A, Wohlsein P, Smits SL, Schipper D, Bestebroer TM, Okba N, Fux R, Bensaid A, Solanes Foz D, Kuiken T, Baumgärtner W, Segalés J, Sutter G, Osterhaus AD. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science. 2016;351(6268):77–81. doi: 10.1126/science.aad1283. [DOI] [PubMed] [Google Scholar]

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