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Molecular structure of coronaviruses and stem cell use in treatment

Year 2021, , 172 - 180, 30.06.2021
https://doi.org/10.19161/etd.950623

Abstract

Coronaviruses were first discovered in the 1930s. The COVID-19 pandemic that emerged after the SARS and MERS outbreaks caused a lot of infections and deaths in a short time. Coronaviruses are viruses with the largest RNA genome. It has a crown appearance under the microscope due to the glycoproteins it contains. Although there are no specific symptoms of COVID-19 infection, fever, cough, sputum, myalgia and headache are the most prominent symptoms. The most widely used method in its diagnosis is the PCR test. One of the treatments tried in COVID-19 infection, for which there is no standard treatment yet, is stem cell-based therapies.
This review will examine the general epidemiology, genomic nature of COVID-19 and the importance of stem cell treatments for COVID-19.

References

  • Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci U S A. 2019; 116 (52): 27142–50.
  • Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog. 2020; 16 (5): 1–24.
  • Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, Rabaan AA, Sah R, Paniz-Mondolfi A, et al. History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic. Infez Med. 2020; 28 (1): 3–5.
  • Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020; 92 (4): 401–2.
  • Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497–506.
  • Johnson M. Wuhan 2019 Novel Coronavirus - 2019-nCoV. Mater Methods. 2020; 10 (JANUARY): 1–5.
  • Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV. Viruses. 2020; 12 (2): 1–8.
  • Deng S-Q, Peng H-J. Clinical Medicine Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020 Feb; 9 (2): 575.; Feb; 9 (2): 575.
  • Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol 2016 Jun; 24 (6): 490-502.
  • Domingo E, Perales C. Viral quasispecies. PLoS Genet. 2019; 15 (10): 1-20.
  • Zhou P, Yang X Lou, 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): 270–3.
  • Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382 (8): 727–33.
  • Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020; 92: 92.
  • 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. www.thelancet.com. 2020; 395: 565.
  • Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. J Virol. 2011 May; 85 (9): 4122–34.
  • Hu B, Ge X, Wang LF, Shi Z. Bat origin of human coronaviruses Coronaviruses: Emerging and re-emerging pathogens in humans and animals Susanna Lau Positive-strand RNA viruses. Virol J. 2015; 12 (1): 1–10.
  • Chan JF, Kok K. Correction to: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan (Emerging Microbes & Infections, (2020), 9, 1, (221-236), 10.1080/22221751.2020.1719902). Emerg Microbes Infect. 2020; 9 (1): 540.
  • Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020; 5 (4): 562–9.
  • Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment Coronavirus (COVID-19). StatPearls. StatPearls Publishing; 2020 . PMID: 32150360; 1-56.
  • Liu DX, Fung TS, Chong KKL, Shukla A, Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Vol. 109, Antiviral Research. Elsevier; 2014. p. 97–109.
  • Pyle CJ, Uwadiae FI, Swieboda DP, Harker JA. Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology. PLoS Pathog. 2017;13(9):1–27.
  • Bennardo F, Buffone C, Giudice A. New therapeutic opportunities for COVID-19 patients with Tocilizumab: Possible correlation of interleukin-6 receptor inhibitors with osteonecrosis of the jaws. Vol. 106, Oral Oncology. Elsevier Ltd; 2020. p. 104659.
  • Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol. 2018 Feb;10(2).
  • Zayed M, Iohara K. Immunomodulation and Regeneration Properties of Dental Pulp Stem Cells: A Potential Therapy to Treat Coronavirus Disease 2019. Cell Transplant. 2020;29:1–9.
  • Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol. 2006; 13 (8): 751–2.
  • Hoffmann M, Kleine-Weber H, Schroeder S, Mü MA, Drosten C, Pö S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–80.
  • Arndt AL, Larson BJ, Hogue BG. A Conserved Domain in the Coronavirus Membrane Protein Tail Is Important for Virus Assembly. J Virol. 2010; 84 (21): 11418–28.
  • Schoeman D, Fielding BC. Coronavirus envelope protein: Current knowledge. Virol J. 2019;16(1):1–22.
  • McBride R, van Zyl M, Fielding BC. The coronavirus nucleocapsid is a multifunctional protein. Viruses. 2014; 6 (8): 2991–3018.
  • Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6. Cell Stem Cell 2009; 2; 5 (1): 54-63.
  • Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Aug; 71 (15): 762–8.
  • Jiang D, Muschhammer J, Qi Y, Kügler A, De Vries JC, Saffarzadeh M, et al. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells HHS Public Access. Stem Cells. 2016; 34 (9): 2393–406.
  • Braza F, Dirou S, Forest V, Sauzeau V, Hassoun D, Chesné J, et al. Mesenchymal Stem Cells Induce Suppressive Macrophages Through Phagocytosis in a Mouse Model of Asthma. Stem Cells. 2016 Jul; 34 (7): 1836–45.
  • Gao P, Yang X, Mungur L, Kampo S, Wen Q. SuppleAdipose tissue-derived stem cells attenuate acute lung injury through eNOS and eNOS-derived NO. Int J Mol Med. 2013 Jun; 31 (6): 1313–8.
  • Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee JW, et al. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol - Lung Cell Mol Physiol. 2012 May; 302 (10).
  • Khatri M, Richardson LA, Meulia T. Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res Ther. 2018 Jan; 9 (1).
  • Behnke J, Kremer S, Shahzad T, Chao C-M, Böttcher-Friebertshäuser E, Morty RE, et al. MSC Based Therapies—New Perspectives for the Injured Lung. J Clin Med. 2020 Mar; 9 (3): 682.
  • Huppert LA, Matthay MA. Alveolar fluid clearance in pathologically relevant conditions: In vitro and in vivo models of acute respiratory distress syndrome. Front Immunol. 2017; 8 (APR): 1–6.
  • Shah TG, Predescu D, Predescu S. Mesenchymal stem cells-derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options. Clin Transl Med. 2019; 8 (1): 25.
  • Golchin A, Farahany TZ. Biological Products: Cellular Therapy and FDA Approved Products. Vol. 15, Stem Cell Reviews and Reports. Humana Press Inc.; 2019. p. 166–75.
  • Atluri S, Manchikanti L, Hirsch JA. Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ILL COVID-19 patients: The case for compassionate use. Pain Physician. 2020; 23 (2): E71–84.
  • Manchikanti L, Centeno CJ, Atluri S, Albers SL, Shapiro S, Malanga GA, et al. Bone marrow concentrate (BMC) therapy in musculoskeletal disorders: Evidence-based policy position statement of american society of interventional pain physicians (ASIPP). Pain Physician. 2020; 23 (2): E85–131.
  • Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar; 11 (2): 216.
  • Rogers CJ, Harman RJ, Bunnell BA, Schreiber MA, Xiang C, Wang FS, et al. Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients. J Transl Med. 2020; 18 (1): 1–19.
  • Liang B, Chen J, Li T, Wu H, Yang W, Li Y, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine (Baltimore). 2020 Jul; 99 (31): e21429.
  • Shetty AK. Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19)-induced pneumonia. Aging Dis. 2020; 11 (2): 462–4.
  • WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard [Internet]. [cited 2021 Mar 20]. Available from: https://covid19.who.int/
  • Covid19 [Internet]. [cited 2021 Mar 20]. Available from: https://covid19.saglik.gov.tr/

Koronavirüslerin moleküler yapısı ve tedavide kök hücre kullanımı

Year 2021, , 172 - 180, 30.06.2021
https://doi.org/10.19161/etd.950623

Abstract

Koronavirüsler ilk olarak 1930'larda keşfedilmiştir. SARS ve MERS salgınlarından sonra ortaya çıkan COVID-19 pandemisi kısa sürede çok fazla enfeksiyon ve ölüme neden oldu. Koronavirüsler en büyük RNA genomuna sahip virüslerdir. İçerdiği glikoproteinlerden kaynaklı mikroskop altında taç görünümüne sahiptir. COVID-19 enfeksiyonunun spesifik semptomları olmamasına rağmen ateş, öksürük, balgam, miyalji ve baş ağrısı en belirgin semptomlarıdır. Teşhisinde en yaygın kullanılan yöntem PCR testidir. Henüz standart bir tedavisi bulunmayan COVID-19 enfeksiyonunda denenen tedavilerden biri de kök hücre tabanlı tedavilerdir.
Bu derlemede COVID-19'un genel epidemiyolojisi, genomik yapısı ve COVID-19 için kök hücre tedavilerinin önemi irdelenecektir.

References

  • Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci U S A. 2019; 116 (52): 27142–50.
  • Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog. 2020; 16 (5): 1–24.
  • Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, Rabaan AA, Sah R, Paniz-Mondolfi A, et al. History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic. Infez Med. 2020; 28 (1): 3–5.
  • Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020; 92 (4): 401–2.
  • Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497–506.
  • Johnson M. Wuhan 2019 Novel Coronavirus - 2019-nCoV. Mater Methods. 2020; 10 (JANUARY): 1–5.
  • Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV. Viruses. 2020; 12 (2): 1–8.
  • Deng S-Q, Peng H-J. Clinical Medicine Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020 Feb; 9 (2): 575.; Feb; 9 (2): 575.
  • Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol 2016 Jun; 24 (6): 490-502.
  • Domingo E, Perales C. Viral quasispecies. PLoS Genet. 2019; 15 (10): 1-20.
  • Zhou P, Yang X Lou, 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): 270–3.
  • Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382 (8): 727–33.
  • Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020; 92: 92.
  • 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. www.thelancet.com. 2020; 395: 565.
  • Glowacka I, Bertram S, Muller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. J Virol. 2011 May; 85 (9): 4122–34.
  • Hu B, Ge X, Wang LF, Shi Z. Bat origin of human coronaviruses Coronaviruses: Emerging and re-emerging pathogens in humans and animals Susanna Lau Positive-strand RNA viruses. Virol J. 2015; 12 (1): 1–10.
  • Chan JF, Kok K. Correction to: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan (Emerging Microbes & Infections, (2020), 9, 1, (221-236), 10.1080/22221751.2020.1719902). Emerg Microbes Infect. 2020; 9 (1): 540.
  • Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020; 5 (4): 562–9.
  • Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment Coronavirus (COVID-19). StatPearls. StatPearls Publishing; 2020 . PMID: 32150360; 1-56.
  • Liu DX, Fung TS, Chong KKL, Shukla A, Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Vol. 109, Antiviral Research. Elsevier; 2014. p. 97–109.
  • Pyle CJ, Uwadiae FI, Swieboda DP, Harker JA. Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology. PLoS Pathog. 2017;13(9):1–27.
  • Bennardo F, Buffone C, Giudice A. New therapeutic opportunities for COVID-19 patients with Tocilizumab: Possible correlation of interleukin-6 receptor inhibitors with osteonecrosis of the jaws. Vol. 106, Oral Oncology. Elsevier Ltd; 2020. p. 104659.
  • Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol. 2018 Feb;10(2).
  • Zayed M, Iohara K. Immunomodulation and Regeneration Properties of Dental Pulp Stem Cells: A Potential Therapy to Treat Coronavirus Disease 2019. Cell Transplant. 2020;29:1–9.
  • Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol. 2006; 13 (8): 751–2.
  • Hoffmann M, Kleine-Weber H, Schroeder S, Mü MA, Drosten C, Pö S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–80.
  • Arndt AL, Larson BJ, Hogue BG. A Conserved Domain in the Coronavirus Membrane Protein Tail Is Important for Virus Assembly. J Virol. 2010; 84 (21): 11418–28.
  • Schoeman D, Fielding BC. Coronavirus envelope protein: Current knowledge. Virol J. 2019;16(1):1–22.
  • McBride R, van Zyl M, Fielding BC. The coronavirus nucleocapsid is a multifunctional protein. Viruses. 2014; 6 (8): 2991–3018.
  • Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6. Cell Stem Cell 2009; 2; 5 (1): 54-63.
  • Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Aug; 71 (15): 762–8.
  • Jiang D, Muschhammer J, Qi Y, Kügler A, De Vries JC, Saffarzadeh M, et al. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells HHS Public Access. Stem Cells. 2016; 34 (9): 2393–406.
  • Braza F, Dirou S, Forest V, Sauzeau V, Hassoun D, Chesné J, et al. Mesenchymal Stem Cells Induce Suppressive Macrophages Through Phagocytosis in a Mouse Model of Asthma. Stem Cells. 2016 Jul; 34 (7): 1836–45.
  • Gao P, Yang X, Mungur L, Kampo S, Wen Q. SuppleAdipose tissue-derived stem cells attenuate acute lung injury through eNOS and eNOS-derived NO. Int J Mol Med. 2013 Jun; 31 (6): 1313–8.
  • Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee JW, et al. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol - Lung Cell Mol Physiol. 2012 May; 302 (10).
  • Khatri M, Richardson LA, Meulia T. Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res Ther. 2018 Jan; 9 (1).
  • Behnke J, Kremer S, Shahzad T, Chao C-M, Böttcher-Friebertshäuser E, Morty RE, et al. MSC Based Therapies—New Perspectives for the Injured Lung. J Clin Med. 2020 Mar; 9 (3): 682.
  • Huppert LA, Matthay MA. Alveolar fluid clearance in pathologically relevant conditions: In vitro and in vivo models of acute respiratory distress syndrome. Front Immunol. 2017; 8 (APR): 1–6.
  • Shah TG, Predescu D, Predescu S. Mesenchymal stem cells-derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options. Clin Transl Med. 2019; 8 (1): 25.
  • Golchin A, Farahany TZ. Biological Products: Cellular Therapy and FDA Approved Products. Vol. 15, Stem Cell Reviews and Reports. Humana Press Inc.; 2019. p. 166–75.
  • Atluri S, Manchikanti L, Hirsch JA. Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ILL COVID-19 patients: The case for compassionate use. Pain Physician. 2020; 23 (2): E71–84.
  • Manchikanti L, Centeno CJ, Atluri S, Albers SL, Shapiro S, Malanga GA, et al. Bone marrow concentrate (BMC) therapy in musculoskeletal disorders: Evidence-based policy position statement of american society of interventional pain physicians (ASIPP). Pain Physician. 2020; 23 (2): E85–131.
  • Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar; 11 (2): 216.
  • Rogers CJ, Harman RJ, Bunnell BA, Schreiber MA, Xiang C, Wang FS, et al. Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients. J Transl Med. 2020; 18 (1): 1–19.
  • Liang B, Chen J, Li T, Wu H, Yang W, Li Y, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine (Baltimore). 2020 Jul; 99 (31): e21429.
  • Shetty AK. Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19)-induced pneumonia. Aging Dis. 2020; 11 (2): 462–4.
  • WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard [Internet]. [cited 2021 Mar 20]. Available from: https://covid19.who.int/
  • Covid19 [Internet]. [cited 2021 Mar 20]. Available from: https://covid19.saglik.gov.tr/
There are 48 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Reviews
Authors

Meliz Sofu 0000-0001-6106-2203

Canberk Tomruk 0000-0002-3810-3705

Hatice Kübra Başaloğlu 0000-0002-0594-6773

Emel Öykü Çetin Uyanıkgil 0000-0001-8822-9130

Yiğit Uyanıkgil 0000-0002-4016-0522

Publication Date June 30, 2021
Submission Date March 21, 2021
Published in Issue Year 2021

Cite

Vancouver Sofu M, Tomruk C, Başaloğlu HK, Çetin Uyanıkgil EÖ, Uyanıkgil Y. Koronavirüslerin moleküler yapısı ve tedavide kök hücre kullanımı. ETD. 2021;60(2):172-80.

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