Sidhant JAİN, Meenakshi RANA, Pooja JAİN

Emergence, Evolution and Economics of Coronaviruses

Viruses are the most abundant biological entities on our planet. On the basis of parameters like capsid structure, morphology, genetic material, etc., they are classified into different families. The Coronaviridae family of viruses includes a diverse group of positive strand RNA viruses and a subset of these viruses infects humans. Though some of these human-infecting coronaviruses cause minor respiratory ailments in healthy adults but three of them are responsible for major pandemics of the 21st century. These pandemics claimed thousands to several hundred thousands of human lives and have plunged the regional economies and even the global economy into an abyss. This work highlights the current research on human coronaviruses involving their diversity, evolution, clinical, and zoonotic attributes. An economic impact analysis of major coronaviruses is also presented to point out how these pathogens have claimed billions of dollars.

Keywords:

ACE-2 receptor, Coronaviridae, Coronaviruses, COVID-19 Evolution, MERS, SARS,

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1. Koonin EV, Dolja, VV. A virocentric perspective on the evolution of life. Curr Opin Virol 2013; 3(5): 546-57. google scholar
2. Koonin EV, Senkevich TG, Dolja VV. Compelling reasons why viruses are relevant for the origin of cells. Nat Rev Microbiol 2009;7(8):615. google scholar
3. Wessner DR. The origins of viruses. Nature Education 2010; 3(9): 37. google scholar
4. Durzynska J, Gozdzicka-Jözefiak A. Viruses and cells intertwined since the dawn of evolution. Virol J 2015; 12: 169. google scholar
5. Geller C, Varbanov M, Duval RE. Human coronaviruses: insights into environmental resistance and its influence on the develop-ment of new antiseptic strategies. Viruses 2012; 4(11): 3044-68. google scholar
6. Fan Y, Zhao K, Shi ZL, Zhou, P. Bat coronaviruses in China. Viruses 2019; 11(3). google scholar
7 LeDuc JW, Barry MA SARS, the first pandemic of the 21st Century Emerg Infect Dis 2004; 10(11): e26 google scholar
8 Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al Epidemiology, ge-netic recombination, and pathogenesis of coronaviruses Trends Microbiol 2016; 24(6): 490-502 google scholar
9 Forni D, Cagliani R, Clerici M, Sironi M Molecular evolution of hu-man coronavirus genomes Trends Microbiol 2017; 25(1): 35-48 google scholar
10 Cui J, Li F, Shi ZL Origin and evolution of pathogenic coronavirus-es Nat Rev Microbiol 2019; 17(3): 181-92 google scholar
11 Schalk AF, Hawn MC An apparently new respiratory disease of baby chicks J Amer vet med Ass 1931; 78: 413-22 google scholar
12 McIntosh K Coronaviruses: a comparative review Curr Top Micro-biol Immunol 1974; 63: 85-129 google scholar
13 Tyrrell DA, Bynoe ML Cultivation of a novel type of common-cold virus in organ cultures Br med J 1965; 1(5448): 1467-70 google scholar
14 Woo PC, Lau S K, Lam CS, Lau CC, Tsang AK, Lau JH, et al Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus J Virol 2012; 86(7): 3995-4008 google scholar
15 Wertheim JO, Chu DK, Peiris JS, Kosakovsky Pond S L, Poon LL A case for the ancient origin of coronaviruses J Virol 2013; 87(12): 7039-45 google scholar
16 . Huang YW, Dickerman AW, Pineyro P, Li L, Fang L, Kiehne R . Origin, evolution, and genotyping of emergent porcine epidemic diar-rhea virus strains in the United States. mBio 2013; 4(5): e00737-13. google scholar
17. Ma Y, Zhang Y, Liang X, Lou F, Oglesbee M, Krakowka S, et al. Origin, evolution, and virulence of porcine deltacoronaviruses in the Unit-ed States. mBio 2015; 6(2): e00064. google scholar
18. Guo Y, Cao Q, Hong Z, Tan Y, Chen S, Jin H. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) out-break - an update on the status. Military Med Res 2020; 7:11. google scholar
19. Hamre D, Procknow JJ. A new virus isolated from the human respi-ratory tract. Proc Soc Exp Biol Med 1966; 121(1): 190-3. google scholar
20. Bradburne AF, Bynoe ML, Tyrrell DA. Effects of a “new” human re-spiratory virus in volunteers. Br Med J 1967; 3(5568): 767-9. google scholar
21. Gagneur A, Vallet S, Talbot PJ, Legrand-Quillien M, Picard B, Payan C, et al. Outbreaks of human coronavirus in a pediatric and neona-tal intensive care unit. Eur J Pediatr 2018; 167(12): 1427-34. google scholar
22. Vassilara F, Spyridaki A, Pothitos G, Deliveliotou A, Papadopoulos A. A rare case of human coronavirus 229E associated with acute respiratory distress syndrome in a healthy adult. Case Rep Infect Dis 2018. google scholar
23. Tao Y, Shi M, Chommanard C, Queen K, Zhang J, Markotter W, et al. Surveillance of bat coronaviruses in Kenya identifies relatives of human coronaviruses NL63 and 229E and their recombination history. J Virol 2017; 91(5): e01953-16. google scholar
24. Corman VM, Eckerle I, Memish ZA, Liljander AM, Dijkman R, Jons-dottir H, et al. Link of a ubiquitous human coronavirus to drome-dary camels. Proc Natl Acad Sci U S A 2016; 113(35): 9864-9. google scholar
25. Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, et al. The human coronavirus HCoV-229E S-protein structure and recep-tor binding. Elife 2019; 8: 51230. google scholar
26. Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT, et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357(6377): 420-2. google scholar
27. Van der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJ, Wolthers KC, et al. Identification of a new human coronavirus. Nat Med 2004; 10(4): 368-73. google scholar
28. Van der Hoek L, Pyrc K, Berkhout B. Human coronavirus NL63, a new respiratory virus. FEMS Microbiol Rev 2006; 30(5): 760-73. google scholar
29. Abdul-Rasool S, Fielding BC. Understanding human coronavirus HCoV-NL63. Open Virol J 2010; 4: 76-84. google scholar
30. Bastien N, Anderson K, Hart L, Van Caeseele P, Brandt K, Milley D, et al. Human coronavirus NL63 infection in Canada. J Infect Dis 2005; 191(4): 503-6. google scholar
31. Ye ZW, Yuan S, Yuen KS, Fung SY, Chan CP, Jin DY. Zoonotic origins of human coronaviruses. Int J Biol Sci 2020; 16(10): 1686-97. google scholar
32. Hofmann H, Pyrc K, Van der Hoek L, Geier M, Berkhout B, Pöhlmann S. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci USA 2005; 102(22): 7988-93. google scholar
33. McIntosh K, Becker W, Chanock R. Growth in suckling-mouse brain of''IBV-Like"viruses from patients with upper respiratorytractdis-ease. Proc Natl Acad Sci USA 1967; 58(6): 2268- 73. google scholar
34. Wevers BA, Van der Hoek L. Recently discovered human coronavi-ruses. Clin Lab Med 2009; 29(4): 715-24. google scholar
35. Jean A, Quach C, Yung A, Semret M. Severity and outcome asso-ciated with human coronavirus OC43 infections among children. Pediatr Infect Dis J 2013; 32(4): 325-9. google scholar
36. Vijgen L, Keyaerts E, Moes E, Thoelen I, Wollants E, Lemey P, et al. Complete genomic sequence of human coronavirus OC43: molec-ular clock analysis suggests a relatively recent zoonotic coronavi-rus transmission event. J Virol 2005; 79(3): 1595-1604. google scholar
37. Jonsdottir HR, Dijkman R. Coronaviruses and the human airway: a universal system for virus-host interaction studies. Virol J 2016; 13: 24. google scholar
38. Owczarek K, Szczepanski A, Milewska A, Baster Z, Rajfur Z, Sarna M, et al. Early events during human coronavirus OC43 entry to the cell. Sci Rep 2018; 8(1): 7124. google scholar
39. Woo PC, Lau SK, Chu CM, Chan KH, Tsoi HW, Huang Y, et al. Charac-terization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol 2005; 79(2): 884-95. google scholar
40. WHO: https://who.int/csr/don/2004_05_18a/en/ (Last accessed: 3rd Nov., 2021) google scholar
41. Hu B, Zeng LP, Yang XL, Ge XY, Zhang W, Li B, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 2017; 13(11): e1006698. google scholar
42. Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as caus-es of pneumonia. Respirology 2018; 23(2): 130-7. google scholar
43. Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 2019; 11(1): 59. google scholar
44. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angio-tensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4. google scholar
45. Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 2004; 101(44): 15748-53. google scholar
46. Guo Y, Korteweg C, McNutt MA, GU J. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res 2008; 133(1): 4-12. google scholar
47. Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, et al. Organ distribu-tion of severe acute respiratory syndrome (SARS) associated coro-navirus (SARS-CoV) in SARS patients: implications for pathogene-sis and virus transmission pathways. J Pathol 2004; 203(2): 622-30. google scholar
48. WHO: https://www.who.int/csr/sars/country/table2004_04_21/ en/ (Last accessed: 3rd March, 2022). google scholar
49. WHO: https://www.who.int/emergencies/mers-cov/en/ (Last ac-cessed: 3rd March, 2022). google scholar
50. Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East re-spiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin. Microbiol Rev 2005; 28(2): 465-522. google scholar
51. Corman VM, Ithete NL, Richards LR, Schoeman MC, Preiser W, Dro-sten C, et al. Rooting the phylogenetic tree of Middle east respi-ratory syndrome coronavirus by characterization of a conspecific virus from an African bat. J Virol 2014; 88(19): 11297-303. google scholar
52. Yang L, Wu Z, Ren X, Yang F, Zhang J, He G, et al. MERS-related betacoronavirus in Vespertilio superans bats, China. Emerg Infect Dis 2014; 20(7): 1260-2. google scholar
53. Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R, et al. Middle East respiratory syndrome coronavirus in drome-dary camels: an outbreak investigation. Lancet Infect dis 2014; 14(2): 140-5. google scholar
54. Hijawi B, Abdallat M, Sayaydeh A, Alqasrawi S, Haddadin A, Jaarour N, et al. Novel coronavirus infections in Jordan, April 2012: epide-miological findings from a retrospective investigation. East Medi-terr Health J 2013; 19(1): S12-18. google scholar
55. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, et al. Epidemiological, demographic, and clinical char-acteristics of 47 cases of Middle east respiratory syndrome corona-virus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 2013; 13(9): 752-61. google scholar
56. Arwady MA, Alraddadi B, BaslerC, Azhar EI, Abuelzein E, Sindy AI, et al. Middle east respiratory syndrome coronavirus transmission in extended family, Saudi Arabia, 2014. Emerg Infect Dis 2016; 22(8): 1395-402. google scholar
57. Korean Centres for Disease Control and Prevention. Middle east re-spiratory syndrome coronavirus outbreak in the Republic of Korea. Osong Public Health Res Perspect 2015; 6(4): 269-78. google scholar
58. Hunter J, Nguyen D, AdenB, Al Bandar Z, Al Dhaheri W, Abu Elkheir K. Transmission of middle east respiratory syndrome coronavirus infections in healthcare settings, Abu Dhabi. Emerg Infect Dis 2016; 22(4): 647-56. google scholar
59. Moon SY, Son JS. Infectivity of an asymptomatic patient with mid-dle east respiratory syndrome coronavirus infection. Clin Infect Dis 2017; 64(10): 1457-8. google scholar
60. 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 2016; 186(1): 7886. google scholar
61. Widagdo W, Raj VS, Schipper D, Kolijn K, Leenders GJLH, Bosch BJ, et al. Differential expression of the middle east respiratory syn-drome coronavirus receptor in the upper respiratory tracts of hu-mans and dromedary camels. J Virol 2016; 90: 4838-42. google scholar
62. Lambeir AM, Durinx C, Scharpe S, De Meester I. Dipeptidyl-pepti-dase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 2003; 40(3): 209-94. google scholar
63. Chu H, Zhou J, Wong BH, Li C, Chan JF, Cheng ZS, et al. Middle east respiratory syndrome coronavirus efficiently infects human prima-ry T lymphocytes and activates the extrinsic and intrinsic apopto-sis pathways. J Infect Dis 2016; 213(6): 904-14. google scholar
64. WHO: https://www.who.int/emergencies/mers-cov/en/ (Last ac-cessed: 8th May, 2022). google scholar
65. Engelbrecht FA, Scholes RJ. Test for Covid-19 seasonality and the risk of second waves. One Health 2021; 12: 100202. google scholar
66. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in Chi-na: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA 2020; 323(13): 123942. google scholar
67. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneu-monia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3. google scholar
68. Temmem S, Vongphayloth K, Salazar EB, Munier S, Bonomi M, Reg-nault B, et al. Coronaviruses with a SARS-CoV-2-like receptor-bind-ing domain allowing ACE2-mediated entry into human cells iso-lated from bats of Indochinese peninsula. Pre-print. 2021. DOI: 10.21203/rs.3.rs-871965/v1 google scholar
69. Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, et al. Iden-tifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature 2020; 583(7815), 282-5. google scholar
70. Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 2020; 583(7815): 286-9. google scholar
71. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and di-vergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS- CoV-2. J. Med. Virol 2020; 92(6): 595-60. google scholar
72. Ji W, Wang W, Zhao X, Zai J, Li X. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol 2020; 92(4): 433-40. google scholar
73. Luan J, Jin X, Lu Y, Zhang L. SARS-CoV-2 spike protein favors ACE2 from Bovidae and Cricetidae. J Med Virol 2020; 92(9): 1649-56. google scholar
74. Zheng J. SARS-CoV-2: an Emerging coronavirus that causes a global threat. Int J Biol Sci 2020; 16(10): 1678-85. google scholar
75. Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, et al. Presumed asymptom-atic carrier transmission of COVID-19. JAMA 2020; 323(14): 1406-7. google scholar
76. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV Infection from an asymptomatic contact in Germany. N Engl J Med 2020; 382(10): 970-1. google scholar
77. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Suscep-tibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science 2020; 368(6494): 1016- 20. google scholar
78. Do Vale B, Lopes AP, Fontes M, Silvestre M, Cardoso L, Coelho AC. Bats, pangolins, minks and other animals - villains or victims of SARS-CoV-2? Vet Res Commun 2021; 45(1): 1-19.
google scholar
79. Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 2020; 9(1): 386-9. google scholar
80. Worldometer: https://www.worldometers.info/coronavirus/ (Last accessed: 8th May, 2022). google scholar
81. Forni G, Mantovani A, COVID-19 Commission of Accademia Nazi-onale dei Lincei, Rome. COVID-19 vaccines: where we stand and challenges ahead. Cell Death Differ 2021; 28(2): 626-39. google scholar
82. Qiu W, Chu C, Mao A, Wu J. The impacts on health, society, and economy of SARS and H7N9 outbreaks in China: A case compari-son study. J Environ Public Health 2018; 2710185. google scholar
83. Siu A, Richard Wong YCR. Economic impact of SARS: The case of Hong Kong. Asian Economic Papers 2004; 3(1): 62-83. google scholar
84. AlRuthia Y, Somily AM, Alkhamali AS, Bahari OH, AlJuhani RJ, Alse-naidy M, et al. Estimation of direct medical costs of middle east respiratory syndrome coronavirus infection: A single-center retro-spective chart review study. Infect Drug Resist 2019; 12: 3463-73. google scholar
85. Joo H, Maskery BA, Berro AD, Rotz LD, Lee YK, Brown CM. Economic Impact of the 2015 MERS Outbreak on the Republic of Korea’s tour-ism-related industries. Health Secur 2019; 17(2): 100-8. google scholar
86. Aljazeera:https://www.aljazeera.com/ajimpact/imf-covid-19-global-recession-2020-200323231228113.html (Last accessed: 3rd Nov., 2021). google scholar
87. Nicola M, Alsafi Z, Sohrabi C, Kerwan A, Al-Jabir A, Iosifidis C, et al. The socio-economic implications of the coronavirus pandemic (COVID-19): A review. Int J Surg 2020; 78: 185-93. google scholar
88. IMF: https://blogs.imf.org/2020/04/14/the-great-lockdown-worst-economic-downturn-since-the-great-depression/ (Last accessed: 3rd Nov., 2021). google scholar
89. Koonpaew S, Teeravechyan S, Frantz PN, Chailangkarn T, Jong-kaewwattana A. PEDV and PDCoV Pathogenesis: The interplay between host innate immune responses and porcine enteric coro-naviruses. Front Vet Sci 2019; 6: 34. google scholar
90. Sun RQ, Cai RJ, Chen YQ, Liang PS, Chen DK, Song CX. Outbreak of porcine epidemic diarrhea in suckling piglets, China. Emerg Infect Dis 2012; 18(1): 161-3. google scholar
91. Paarlberg PL. Updated estimated economic welfare impacts of porcine epidemic diarrhea virus (PEDV). Purdue University, De-partment of Agricultural Economics, Working Papers 2014; 14: 1-38. google scholar
92. Jung K, Hu H, Saif LJ. Porcine deltacoronavirus infection: Etiology, cell culture for virus isolation and propagation, molecular epide-miology and pathogenesis. Virus Res 2016; 226: 50-9. google scholar
93. Ignjatovic J, Sapats S. Avian infectious bronchitis virus. Rev Sci Tech 2000; 19(2): 493-508. google scholar
94. Colvero LP, Villarreal LY, Torres CA, Brando PE. Assessing the eco-nomic burden of avian infectious bronchitis on poultry farms in Brazil. Rev Sci Tech 2015; 34(3): 993-9. google scholar
95. Gomaa MH, Yoo D, Ojkic D, Barta JR. Seroprevalence of turkey coronavirus in North American turkeys determined by a newly de-veloped enzyme-linked immunosorbent assay based on recombi-nant antigen. Clin Vaccine Immunol 2008; 15(12): 1839-44. google scholar
96. Woo PC, Lau SK, Yuen KY. Clinical features and molecular epide-miology of coronavirus-HKU1-associated community-acquired pneumonia. Hong Kong Med J 2009; 15(9): 46-7. google scholar
97. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli C. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis 2020; 20(9): e238-44. google scholar
98. Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis 2020; 26(7). google scholar
99. Chu DKW, Hui KPY, Perera RAPM, Miguel E, Niemeyer D, Zhao J, et al. MERS coronaviruses from camels in Africa exhibit region-de-pendent genetic diversity. Proc Natl Acad Sci U S A 2018; 115(12): 3144-9. google scholar
100. Wang L, Byrum B, Zhang Y. Porcine coronavirus HKU15 detected in 9 US states, 2014. Emerg Infect Dis 2014; 20(9): 1594-5. google scholar
101. Zhai SL, Wei WK, Li XP, Wen XH, Zhou X, Zhang H, et al. Occurrence and sequence analysis of porcine deltacoronaviruses in southern China. Virol J 2016; 13: 136. google scholar
102. Zhou P, Fan H, Lan T, Yang XL, Shi WF, Zhang W. Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 2018; 556(7700): 255-8. google scholar
103. Pfefferle S, Oppong S, Drexler JF, Gloza-Rausch F, Ipsen A, Seebens A, et al. Distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229E in bats, Ghana. Emerg Infect Dis 2009; 15(9): 1377-84. google scholar
104. Al-Khannaq MN, Ng KT, Oong XY, Pang YK, Takebe Y, Chook JB. Mo-lecular epidemiology and evolutionary histories of human corona-virus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia. Virol J 2016; 13: 33. google scholar
105. Huynh J, Li S, Yount B, Smith A, Sturges L, Olsen JC, et al. Evidence supporting a zoonotic origin of human coronavirus strain NL63. J Virol 2012; 86(23): 12816-25. google scholar
106. Hon CC, Lam TY, Shi ZL, Drummond A J, Yip CW, Zeng F. Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus. J Virol 2008; 82(4): 1819-26. google scholar
107. Vijaykrishna D, Smith GJ, Zhang JX, Peiris JS, Chen, H Guan, Y. Evo-lutionary insights into the ecology of coronaviruses. J Virol 2007; 81(8): 4012-20. google scholar
108. Zhang Z, Shen L, Gu, X. Evolutionary Dynamics of MERS-CoV: Po-tential recombination, positive selection and transmission. Sci dRep 2016; 6: 25049. google scholar