Molecular Structure and Genomic Characterization of The New Coronavirus (Covid-19)

Yıl 2020, Cilt: 3 Sayı: 2, 61 - 71, 10.07.2020

Gözde Öztan , Halim İşsever

Öz

SARS-CoV-2, transmitted from person to person and associated with the outbreak of atypical pneumonia, first emerged in Wuhan, China. Although bats, SARS-CoV and MERS-CoV are the primary reservoirs for COVID-19, it turns out that SARS-CoV may have been transmitted from the civet in China, MERS-CoV from camels in the Middle East, and COVID-19 from the bat to humans via the pangolin (scaly anteater). SARS-CoV, MERS-CoV and SARS-CoV-2 are coronaviruses belonging to the Coronaviridae family and Betacoronavirus genus, which cause epidemiological outbreaks, are enveloped viruses with approximately 32 Kb long positive sense, ssRNA, and play a role in the pathogenesis of proinflammatory responses with high mortality rates associated with infection. The 2019-nCoV genome has 89% nucleotide identity with bat SARS-like CoVZXC21 and 82% with human SARS-CoV. ACE2 is the receptor of this severe acute respiratory syndrome coronavirus. The aim of this review is to reveal the molecular structure and genetic features of the SARS-CoV-2 virus and the clinical effects of the disease, which causes COVID-19 acute respiratory disease, and to compare it to SARS and MERS. Clarifying the specific molecular details of COVID-19 will guide researchers to the discovery of its treatment. Thus, the development of the molecular genetic methods for COVID-19 will increase our control measures against the virus in the future.

Anahtar Kelimeler

COVID-19, novel coronavirus, ACE2, spike protein

Yeni Koronavirüsün (Covid-19) Moleküler Yapısı ve Genomik Karakterizasyonu

Öz

İnsandan insana bulaşan ve atipik pnömoni salgınıyla ilişkili yeni bir şiddetli akut solunum sendromu koronavirüs 2 (SARS-CoV-2), Çin'in Wuhan şehrinde ortaya çıkmıştır. Yarasalar, SARS-CoV, MERS-CoV ve COVID-19 için birincil rezervuar olsa da, SARS-CoV’nin, Çin'deki misk kedilerinden, MERS-CoV’nin, Orta Doğu'daki develerden, COVID-19’un yarasadan insana pangolin (pullu karıncayiyen) aracılığıyla bulaşmış olabileceği ortaya çıkmıştır. Epidemiyolojik salgınlara yol açan koronavirüs ailesine ve betakoronavirüs cinsine ait üç insan koronavirüsü (SARS-CoV, MERS-CoV ve SARS-CoV-2) yaklaşık 32 Kb uzunluğunda pozitif anlamlı tek iplikli RNA'sı olan zarflı virüslerden olup enfeksiyonla ilişkili yüksek mortalite oranlarıyla proenflamatuar yanıtların patogenezinde rol oynamaktadırlar. 2019-nCoV genomu, yarasa SARS benzeri CoVZXC21 ile % 89 ve insan SARS-CoV'siyle % 82 nükleotid benzerliğine sahiptir. Orf1a/b, spike, zarf, membran ve nükleoproteinlerinin filogenetik ağaçları yarasa, misk kedisi ve insan SARS koronavirüslerininkiyle yakından ilişkilidir. Anjiyotensin-I dönüştürücü enzim 2 (ACE2), şiddetli akut solunum sendromu koronavirüsünün reseptörüdür. Viral protein ve ACE2 reseptörü arasındaki etkileşim, replikasyon döngüsünde önemli bir adımdır. Bu derlemenin amacı SARS ve MERS ile karşılaştırıldığında COVID-19 akut solunum yolu hastalığına neden olan SARS-CoV-2 virüsünün moleküler yapısı ve genetik özellikleriyle hastalığın klinik etkilerini ortaya koymaktır. COVID-19’un spesifik moleküler detaylarının açıklığa kavuşturulması, tedavi hedeflerine ulaşılmasında yol gösterici olacaktır. Böylelikle COVID-19 için moleküler genetik yöntemlerin geliştirilmesi gelecekte virüse karşı kontrol önlemlerimizi arttıracaktır.

Anahtar Kelimeler

COVID-19, yeni koronavirüs, ACE2, spike protein

Kaynakça

• 1. Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging 2020;47(5):1275-280.
• 2. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579(7798):270-73.
• 3. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63(3):364-74.
• 4. Al-Tawfiq JA, Zumla A, Memish ZA. Travel implications of emerging coronaviruses: SARS and MERS-CoV. Travel Med Infect Dis 2014;12(5):422-8.
• 5. Sutton TC, Subbarao K. Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus. Virology 2015;479480:247-58.
• 6. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019; J Clin Invest 2020; 130(5):2620-9. doi: 10.1172/ JCI137244.
• 7. Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr 2020;87(4):281–6.
• 8. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020;1–9. doi: 10.1002/jmv.25748.
• 9. Huentelman MJ, Zubcevic J, Hernández Prada JA, Xiao X, Dimitrov DS, Raizada MK, et al. Structure-Based Discovery of a Novel Angiotensin-Converting Enzyme 2 Inhibitor. Hypertension 2004;44(6):903-6.
• 10. Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol Immunol Infect 2020; doi.org/10.1016/j. jmii.2020.03.022. (Epub ahead of print)
• 11. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARSCoV-2 by full-length human ACE2. Science 2020;367(6485):1444-8.
• 12. Weiss SR, Leibowitz JL. Coronavirus Pathogenesis. Adv Virus Res 2011;81:85-164. doi: 10.1016/B978-0-12-385885-6.00009-2
• 13. Lissenberg A, Vrolijk MM, van Vliet AL, Langereis MA, de Groot-Mijnes JD, Rottier PJ, et al. Luxury at a cost? Recombinant mouse hepatitis viruses expressing the accessory hem agglutinin esterase protein display reduced fitness in vitro. J Virol 2005;79:15054-63.
• 14. Graham RL, Baric RS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol 2010; 84 (7):3134-46.
• 15. de Haan CA, de Wit M, Kuo L, Montalto-Morrison C, Haagmans BL, Weiss SR, et al. The glycosylation status of the murine hepatitis coronavirus M protein affects the interferogenic capacity of the virus in vitro and its ability to replicate in the liver but not the brain. Virology 2003;312(2): 395-406.
• 16. Ruch TR and Machamer CE. The Coronavirus E Protein: Assembly and Beyond. Viruses 2012;4(3):363-82.
• 17. Escors D, Ortego J, Enjuanes L. The membrane M protein of the transmissible gastroenteritis coronavirus binds to the internal core through the carboxyterminus. Adv Exp Med Biol 2001; 494: 589-93.
• 18. Khailany AR, Safdar M, Ozaslan M. Genomic characterization of a novel SARS-CoV-2. Gene Rep 2020: 1-6.doi: 10.1016/j.genrep.2020.100682
• 19. Wang H, Li X, Li T, Zhang S, Wang L, Wu X, et al. The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur J Clin Microbiol Infect Dis 2020; 24: 1–7. doi: 10.1007/s10096-020-038994 [Epub ahead of print]
• 20. Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem and Biophys Res Commun 2020; 525(1):135-40.
• 21. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395(10224):565-74.
• 22. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DKW, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 2020; 25(3): doi:  10.2807/15607917.ES.2020.25.3.2000045.
• 23. Chan JF, Yip CC, To KK, Tang TH, Wong SC, Leung KH, et al. Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens. J Clin Microbiol 2020;23:58(5) : doi: 10.1128/ JCM.00310-20.
• 24. Tahamtana A, Ardebili A. Real-time RT-PCR in COVID-19 detection: issues affecting the results. Expert Rev Mol Diagn 2020 May;20(5):453-454. doi: 10.1080/14737159.2020.1757437.
• 25. Xiao TA, Tong XY, Zhang S. Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Clin Infec Dis. 2020; doı: 10.1093/cid/ciaa460.
• 26. Pfefferle S, Reucher S, Nörz D, Lütgehetmann M. Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS CoV-2 using a high throughput system. Euro Surveill 2020;25(9):200152. doi: 10.2807/15607917.ES.2020.25.9.2000152
• 27. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 2020;79:104212. doi: 10.1016/j.meegid.2020.104212.
• 28. Licastro D, Rajasekharan S, Dal Monego S, Segat L, D’Agaro P, Marcello A, et al. Isolation and fulllength genome characterization of SARS-CoV-2 from COVID-19 cases in Northern Italy. J Virol 2020; doi: 10.1128/JVI.00543-20. 
• 29. Cleemput S, Dumon W, Fonseca V, Karim WA, Giovanetti M, Alcantara LC, et al. Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes. Bioinformatics 2020; doi: 10.1093/bioinformatics/btaa145.
• 30. Zhong L, Chuan J, Gong BO, Shuai P, Zhou Y, Zhang Y, et al. Detection of serum IgM and IgG for COVID-19 diagnosis. Sci China Life Sci 2020;25 :1–4. doi: 10.1007/s11427-020-1688-9. (Epub ahead of print)
• 31. Guo L, Ren L, Yang S, Xiao M, Chang, Yang F, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis 2020;21: doi: 10.1093/cid/ciaa310.
• 32. Zhou M, Zhang X, Qu J. Coronavirus disease 2019 (COVID-19): a clinical update. Front Med 2020;1-10.doi: 10.1007/s11684-020-0767-8. (Epub ahead of print)
• 33. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis 2020;28: doi: 10.1093/cid/ciaa344.
• 34. Xiang F, Wang X, He X, Peng Z, Yang B, Zhang J, et al. Antibody Detection and Dynamic Characteristics in Patients with COVID-19. Clin Infect Dis 2020; 19: doi: 10.1093/cid/ciaa461. 
• 35. Wu D, Wu T, Liu Q, Yang Z. The SARSCoV-2 outbreak: What we know. Int J Infect Dis 2020;94:44-8. doi: 10.1016/j. ijid.2020.03.004. (Epub ahead of print)
• 36. Chen J. Pathogenicity and transmissibility of 2019-nCoVdA quick overview and comparison with other emerging viruses. Microbes Infect 2020; 22(2):69-71.
• 37. Li G ve De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020;19(3):149-50. 38. Lake MA.What we know so far: COVID-19 current clinical knowledge and research.Clinical Medicine 2020; 20(2):124-7.
• 39. Meethal ME, Ollakkott S, Varma GG. COVID-19 and SARS-CoV-2: Molecular Genetics Perspectives. Indian J Nat Sci 2020; 59(10):18751-18757.
• 40. South AM, Diz DI, Chappell MC. COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol 2020;318(5): doi: 10.1152/ajpheart.00217.2020.