The hallmarks of COVID-19 disease

Autoři: Daolin Tang aff001;  Paul Comish aff002;  Rui Kang aff002
Působiště autorů: The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China aff001;  Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, United States of America aff002
Vyšlo v časopise: The hallmarks of COVID-19 disease. PLoS Pathog 16(5): e1008536. doi:10.1371/journal.ppat.1008536
Kategorie: Review
doi: 10.1371/journal.ppat.1008536


Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety. Analysis of the genetic tree suggests that SARS-CoV-2 belongs to the same Betacoronavirus group as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Although the route for viral transmission remains a mystery, SARS-CoV-2 may have originated in an animal reservoir, likely that of bat. The clinical features of COVID-19, such as fever, cough, shortness of breath, and fatigue, are similar to those of many acute respiratory infections. There is currently no specific treatment for COVID-19, but antiviral therapy combined with supportive care is the main strategy. Here, we summarize recent progress in understanding the epidemiological, virological, and clinical characteristics of COVID-19 and discuss potential targets with existing drugs for the treatment of this emerging zoonotic disease.

Klíčová slova:

Apoptosis – Autophagic cell death – Coronaviruses – Necrotic cell death – Respiratory infections – SARS – Sepsis – SARS coronavirus


1. Perlman S. Another Decade, Another Coronavirus. N Engl J Med. 2020. doi: 10.1056/NEJMe2001126 31978944.

2. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020. doi: 10.1016/S0140-6736(20)30185-9 31986257.

3. Coronaviridae Study Group of the International Committee on Taxonomy of V. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020. doi: 10.1038/s41564-020-0695-z 32123347.

4. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020. doi: 10.1016/S0140-6736(20)30154-9 31986261.

5. 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. doi: 10.1016/S0140-6736(20)30183-5 31986264.

6. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020. doi: 10.1056/NEJMoa2001316 31995857.

7. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020. doi: 10.1016/S0140-6736(20)30211-7 32007143.

8. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020. doi: 10.1001/jama.2020.1585 32031570.

9. 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. doi: 10.1080/22221751.2020.1729071 32065057; PubMed Central PMCID: PMC7048229.

10. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020. doi: 10.1056/NEJMc2004973 32182409.

11. Yang Y, Lu Q, Liu M, Wang Y, Zhang A, Jalali N, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv. 2020; doi: 10.1016/j.cmi.2020.02.005 PubMed PMID: 32058086.

12. Porcheddu R, Serra C, Kelvin D, Kelvin N, Rubino S. Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries. 2020;14(2):125–8. doi: 10.3855/jidc.12600 32146445.

13. Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. 2020. doi: 10.1016/S0140-6736(20)30627-9 32178769.

14. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020. doi: 10.1056/NEJMc2005073 32187458.

15. Schmid MB, Fontijn J, Ochsenbein-Kolble N, Berger C, Bassler D. COVID-19 in pregnant women. Lancet Infect Dis. 2020. doi: 10.1016/S1473-3099(20)30175-4 32197098.

16. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809–15. doi: 10.1016/S0140-6736(20)30360-3 32151335.

17. Team CC-R. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19)—United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(12):343–6. doi: 10.15585/mmwr.mm6912e2 32214079.

18. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020. doi: 10.1056/NEJMoa2002032 32109013.

19. Tang B, Wang X, Li Q, Bragazzi NL, Tang S, Xiao Y, et al. Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions. J Clin Med. 2020;9(2). doi: 10.3390/jcm9020462 32046137; PubMed Central PMCID: PMC7074281.

20. Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know. Int J Infect Dis. 2020. doi: 10.1016/j.ijid.2020.03.004 32171952.

21. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181–92. doi: 10.1038/s41579-018-0118-9 30531947.

22. 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. doi: 10.1056/NEJMoa2001017 31978945.

23. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–9. 10.1038/s41586-020-2008-3 32015508.

24. 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. doi: 10.1016/S0140-6736(20)30251-8 32007145.

25. Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020. doi: 10.1016/j.chom.2020.02.001 32035028.

26. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020. 10.1038/s41586-020-2008-3 32015508.

27. 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. 10.1038/s41586-020-2012-7 32015507.

28. Ji W, Wang W, Zhao X, Zai J, Li X. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Med Virol. 2020. doi: 10.1002/jmv.25682 PubMed PMID: 31967321.

29. Zhang T, Wu Q, Zhang Z. Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Curr Biol. 2020. doi: 10.1016/j.cub.2020.03.022 32197085.

30. Lam TT, Shum MH, Zhu HC, Tong YG, Ni XB, Liao YS, et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020. doi: 10.1038/s41586-020-2169-0 32218527.

31. Mallapaty S. Coronavirus can infect cats—dogs, not so much. Nature. 2020. doi: 10.1038/d41586-020-00984-8 32238897.

32. Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020. doi: 10.1126/science.abb7015 32269068; PubMed Central PMCID: PMC7164390.

33. Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9(1):221–36. doi: 10.1080/22221751.2020.1719902 31987001; PubMed Central PMCID: PMC7067204.

34. Jiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol. 2020. doi: 10.1016/ 32249063.

35. Letko M, Munster V. Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV bioRxiv. 2020; PubMed PMID: 27482393; PubMed Central PMCID: PMC4946667.

36. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–3. doi: 10.1126/science.abb2507 32075877.

37. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020. doi: 10.1038/s41586-020-2179-y 32225175.

38. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020. doi: 10.1038/s41586-020-2180-5 32225176.

39. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020. doi: 10.1016/j.cell.2020.02.058 32155444.

40. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 2020. doi: 10.1126/science.abb2762 32132184.

41. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020. doi: 10.1016/j.cell.2020.02.052 32142651.

42. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020;117(13):7001–3. doi: 10.1073/pnas.2002589117 32165541.

43. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor GRP78 binding site prediction. J Infect. 2020. doi: 10.1016/j.jinf.2020.02.026 32169481.

44. Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. BioRxiv. 2020; doi: 10.18632/aging.102935 PubMed PMID: 32191628.

45. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020. doi: 10.1056/NEJMoa2001191 32004427.

46. Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—an update on the status. Mil Med Res. 2020;7(1):11. doi: 10.1186/s40779-020-00240-0 32169119; PubMed Central PMCID: PMC7068984.

47. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. 2020; doi: 10.1097/HP.0000000000001199 PubMed PMID: 31990783.

48. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020. doi: 10.1056/NEJMoa2001282 32187464.

49. Ren JL, Zhang AH, Wang XJ. Traditional Chinese medicine for COVID-19 treatment. Pharmacol Res. 2020;155:104743. doi: 10.1016/j.phrs.2020.104743 32145402.

50. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020. doi: 10.1016/S0140-6736(20)30628-0 32192578.

51. Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020;19(3):149–50. doi: 10.1038/d41573-020-00016-0 32127666.

52. Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347–64. doi: 10.1038/s41422-019-0164-5 30948788; PubMed Central PMCID: PMC6796845.

53. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2014;505(7484):509–14. doi: 10.1038/nature12940 24356306; PubMed Central PMCID: PMC4047036.

54. Zhu X, Wu T, Chi Y, Ge Y, Wu B, Zhou M, et al. Pyroptosis induced by enterovirus A71 infection in cultured human neuroblastoma cells. Virology. 2018;521:69–76. doi: 10.1016/j.virol.2018.05.025 29886343.

55. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111–6. doi: 10.1038/nature18590 27281216.

56. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535(7610):153–8. doi: 10.1038/nature18629 27383986; PubMed Central PMCID: PMC5539988.

57. Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526(7575):666–71. doi: 10.1038/nature15541 26375259.

58. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–5. Epub 2015/09/17. doi: 10.1038/nature15514 26375003.

59. He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res. 2015;25(12):1285–98. doi: 10.1038/cr.2015.139 26611636; PubMed Central PMCID: PMC4670995.

60. Zhang H, Zeng L, Xie M, Liu J, Zhou B, Wu R, et al. TMEM173 Drives Lethal Coagulation in Sepsis. Cell Host Microbe. 2020;27(4):556–70 e6. doi: 10.1016/j.chom.2020.02.004 32142632.

61. Lieberman J, Wu H, Kagan JC. Gasdermin D activity in inflammation and host defense. Sci Immunol. 2019;4(39). doi: 10.1126/sciimmunol.aav1447 31492708.

62. Kang R, Zeng L, Zhu S, Xie Y, Liu J, Wen Q, et al. Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host Microbe. 2018;24(1):97–108 e4. doi: 10.1016/j.chom.2018.05.009 29937272; PubMed Central PMCID: PMC6043361.

63. Yang X, Cheng X, Tang Y, Qiu X, Wang Y, Kang H, et al. Bacterial Endotoxin Activates the Coagulation Cascade through Gasdermin D-Dependent Phosphatidylserine Exposure. Immunity. 2019;51(6):983–96 e6. doi: 10.1016/j.immuni.2019.11.005 31836429.

64. Hu JJ, Liu X, Zhao J, Xia S, Ruan J, Luo X, et al. Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D. bioRxiv. 2018; doi: 10.1124/mol.64.5.1076 PubMed PMID: 14573756.

65. Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, et al. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res. 2018;150:155–63. doi: 10.1016/j.antiviral.2017.12.015 29289665.

66. Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015;2(12):e520–9. doi: 10.1016/S2352-3018(15)00226-X 26614966; PubMed Central PMCID: PMC5108570.

67. Lee SA, Elliott JH, McMahon J, Hartogenesis W, Bumpus NN, Lifson JD, et al. Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial. Clin Pharmacol Ther. 2019;105(3):692–702. doi: 10.1002/cpt.1220 30137649; PubMed Central PMCID: PMC6379104.

68. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012;249(1):158–75. doi: 10.1111/j.1600-065X.2012.01146.x 22889221; PubMed Central PMCID: PMC3662247.

69. Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139–62. doi: 10.1146/annurev-immunol-030409-101323 21219181; PubMed Central PMCID: PMC4536551.

70. Wang H, Ward MF, Fan XG, Sama AE, Li W. Potential role of high mobility group box 1 in viral infectious diseases. Viral Immunol. 2006;19(1):3–9. doi: 10.1089/vim.2006.19.3 16553546; PubMed Central PMCID: PMC1782047.

71. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285(5425):248–51. doi: 10.1126/science.285.5425.248 10398600.

72. Tsung A, Klune JR, Zhang X, Jeyabalan G, Cao Z, Peng X, et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med. 2007;204(12):2913–23. doi: 10.1084/jem.20070247 17984303; PubMed Central PMCID: PMC2118528.

73. Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, et al. HMGB1 in health and disease. Mol Aspects Med. 2014;40:1–116. doi: 10.1016/j.mam.2014.05.001 25010388; PubMed Central PMCID: PMC4254084.

74. Chen G, Chen DZ, Li J, Czura CJ, Tracey KJ, Sama AE, et al. Pathogenic role of HMGB1 in SARS? Med Hypotheses. 2004;63(4):691–5. doi: 10.1016/j.mehy.2004.01.037 15325019.

75. Wu AH, He L, Long W, Zhou Q, Zhu S, Wang P, et al. Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action. Evid Based Complement Alternat Med. 2015;2015:456305. doi: 10.1155/2015/456305 25821489; PubMed Central PMCID: PMC4363608.

76. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045–6. doi: 10.1016/S0140-6736(03)13615-X 12814717; PubMed Central PMCID: PMC7112442.

77. Yang M, Cao L, Xie M, Yu Y, Kang R, Yang L, et al. Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis. Biochem Pharmacol. 2013;86(3):410–8. doi: 10.1016/j.bcp.2013.05.013 23707973; PubMed Central PMCID: PMC3713089.

78. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69. doi: 10.1186/1743-422X-2-69 16115318; PubMed Central PMCID: PMC1232869.

79. de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014;58(8):4875–84. doi: 10.1128/AAC.03011-14 24841269; PubMed Central PMCID: PMC4136071.

80. Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323(1):264–8. doi: 10.1016/j.bbrc.2004.08.085 15351731.

81. Al-Bari MAA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017;5(1):e00293. doi: 10.1002/prp2.293 28596841; PubMed Central PMCID: PMC5461643.

82. Tsai WP, Nara PL, Kung HF, Oroszlan S. Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses. 1990;6(4):481–9. doi: 10.1089/aid.1990.6.481 1692728.

83. Savarino A, Gennero L, Sperber K, Boelaert JR. The anti-HIV-1 activity of chloroquine. J Clin Virol. 2001;20(3):131–5. doi: 10.1016/s1386-6532(00)00139-6 11166661.

84. Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70(6):1608–21. doi: 10.1093/jac/dkv018 25693996.

85. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. doi: 10.1038/s41422-020-0282-0 32020029.

86. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16. doi: 10.1038/s41421-020-0156-0 32194981; PubMed Central PMCID: PMC7078228.

87. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa237 32150618.

88. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72–3. doi: 10.5582/bst.2020.01047 32074550.

89. multicenter collaboration group of Department of S, Technology of Guangdong P, Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus p. [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(0):E019. doi: 10.3760/cma.j.issn.1001-0939.2020.0019 32075365.

90. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020:105949. doi: 10.1016/j.ijantimicag.2020.105949 32205204; PubMed Central PMCID: PMC7102549.

91. Tang D, Li J, Zhang R, Kang R, Klionsky DJ. Chloroquine in Fighting COVID-19: Good, Bad, or Both? Autophagy. 2020.

92. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus Infections and Immune Responses. J Med Virol. 2020. doi: 10.1002/jmv.25685 31981224.

93. Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet. 2019. doi: 10.1038/s41576-019-0151-1 31358977.

94. Ni G, Ma Z, Damania B. cGAS and STING: At the intersection of DNA and RNA virus-sensing networks. PLoS Pathog. 2018;14(8):e1007148. doi: 10.1371/journal.ppat.1007148 30114241; PubMed Central PMCID: PMC6095619.

95. Sze A, Belgnaoui SM, Olagnier D, Lin R, Hiscott J, van Grevenynghe J. Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis. Cell Host Microbe. 2013;14(4):422–34. doi: 10.1016/j.chom.2013.09.009 24139400.

96. Zhou Q, Lin H, Wang S, Wang S, Ran Y, Liu Y, et al. The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling. Cell Host Microbe. 2014;16(4):450–61. doi: 10.1016/j.chom.2014.09.006 25299331.

97. Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, Moeller HB, et al. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat Immunol. 2012;13(8):737–43. doi: 10.1038/ni.2350 22706339; PubMed Central PMCID: PMC3411909.

98. Franz KM, Neidermyer WJ, Tan YJ, Whelan SPJ, Kagan JC. STING-dependent translation inhibition restricts RNA virus replication. Proc Natl Acad Sci U S A. 2018;115(9):E2058–E67. doi: 10.1073/pnas.1716937115 29440426; PubMed Central PMCID: PMC5834695.

99. Chung KW, Dhillon P, Huang S, Sheng X, Shrestha R, Qiu C, et al. Mitochondrial Damage and Activation of the STING Pathway Lead to Renal Inflammation and Fibrosis. Cell Metab. 2019;30(4):784–99 e5. doi: 10.1016/j.cmet.2019.08.003 31474566.

100. Luo X, Li H, Ma L, Zhou J, Guo X, Woo SL, et al. Expression of STING Is Increased in Liver Tissues From Patients With NAFLD and Promotes Macrophage-Mediated Hepatic Inflammation and Fibrosis in Mice. Gastroenterology. 2018;155(6):1971–84 e4. doi: 10.1053/j.gastro.2018.09.010 30213555; PubMed Central PMCID: PMC6279491.

101. Zhao Q, Wei Y, Pandol SJ, Li L, Habtezion A. STING Signaling Promotes Inflammation in Experimental Acute Pancreatitis. Gastroenterology. 2018;154(6):1822–35 e2. doi: 10.1053/j.gastro.2018.01.065 29425920; PubMed Central PMCID: PMC6112120.

102. Benmerzoug S, Rose S, Bounab B, Gosset D, Duneau L, Chenuet P, et al. STING-dependent sensing of self-DNA drives silica-induced lung inflammation. Nat Commun. 2018;9(1):5226. doi: 10.1038/s41467-018-07425-1 30523277; PubMed Central PMCID: PMC6283886.

103. Hu Q, Ren H, Li G, Wang D, Zhou Q, Wu J, et al. STING-mediated intestinal barrier dysfunction contributes to lethal sepsis. EBioMedicine. 2019;41:497–508. doi: 10.1016/j.ebiom.2019.02.055 30878597; PubMed Central PMCID: PMC6443583.

104. Ge W, Hu Q, Fang X, Liu J, Xu J, Hu J, et al. LDK378 improves micro- and macro-circulation via alleviating STING-mediated inflammatory injury in a Sepsis rat model induced by Cecal ligation and puncture. J Inflamm (Lond). 2019;16:3. doi: 10.1186/s12950-019-0208-0 30820191; PubMed Central PMCID: PMC6378711.

105. Heipertz EL, Harper J, Walker WE. STING and TRIF Contribute to Mouse Sepsis, Depending on Severity of the Disease Model. Shock. 2017;47(5):621–31. doi: 10.1097/SHK.0000000000000771 27755506.

106. Gaidt MM, Ebert TS, Chauhan D, Ramshorn K, Pinci F, Zuber S, et al. The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3. Cell. 2017;171(5):1110–24 e18. doi: 10.1016/j.cell.2017.09.039 29033128; PubMed Central PMCID: PMC5901709.

107. Xie J, Li Y, Shen X, Goh G, Zhu Y, Cui J, et al. Dampened STING-Dependent Interferon Activation in Bats. Cell Host Microbe. 2018;23(3):297–301 e4. doi: 10.1016/j.chom.2018.01.006 29478775.

108. Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016;19(2):181–93. doi: 10.1016/j.chom.2016.01.007 26867177; PubMed Central PMCID: PMC4752723.

109. Zeng L, Kang R, Zhu S, Wang X, Cao L, Wang H, et al. ALK is a therapeutic target for lethal sepsis. Sci Transl Med. 2017;9(412). doi: 10.1126/scitranslmed.aan5689 29046432; PubMed Central PMCID: PMC5737927.

110. WHO. IHR Procedures concerning public health emergencies of international concern (PHEIC). PubMed PMID: 32005722.

111. Schweichel JU, Merker HJ. The morphology of various types of cell death in prenatal tissues. Teratology. 1973;7(3):253–66. doi: 10.1002/tera.1420070306 4807128.

112. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3):486–541. doi: 10.1038/s41418-017-0012-4 29362479; PubMed Central PMCID: PMC5864239.

113. Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. Eur J Biochem. 1998;254(3):439–59. doi: 10.1046/j.1432-1327.1998.2540439.x 9688254.

114. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148(1–2):213–27. doi: 10.1016/j.cell.2011.11.031 22265413.

115. Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A. 2012;109(14):5322–7. doi: 10.1073/pnas.1200012109 22421439; PubMed Central PMCID: PMC3325682.

116. Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, et al. Ferroptosis: process and function. Cell Death Differ. 2016;23(3):369–79. doi: 10.1038/cdd.2015.158 26794443; PubMed Central PMCID: PMC5072448.

117. Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017;171(2):273–85. doi: 10.1016/j.cell.2017.09.021 28985560; PubMed Central PMCID: PMC5685180.

118. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 1999;397(6718):441–6. doi: 10.1038/17135 9989411.

119. Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, et al. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007;131(5):966–79. doi: 10.1016/j.cell.2007.10.040 18045538.

120. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5. doi: 10.1126/science.1092385 15001782.

121. Franko J, Pomfy M, Prosbova T. Apoptosis and cell death (mechanisms, pharmacology and promise for the future). Acta Medica (Hradec Kralove). 2000;43(2):63–8. 10953379.

122. Liu Y, Shoji-Kawata S, Sumpter RM Jr., Wei Y, Ginet V, Zhang L, et al. Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci U S A. 2013;110(51):20364–71. doi: 10.1073/pnas.1319661110 24277826; PubMed Central PMCID: PMC3870705.

123. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1–13. Epub 1989/01/01. doi: 10.1101/sqb.1989.054.01.003 2700931.

124. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991–1045. doi: 10.1146/annurev.iy.12.040194.005015 8011301.

125. Seong SY, Matzinger P. Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol. 2004;4(6):469–78. Epub 2004/06/03. doi: 10.1038/nri1372 [pii]. 15173835.

Článek vyšel v časopise

PLOS Pathogens

2020 Číslo 5
Nejčtenější tento týden
Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Třikrát z interní medicíny
nový kurz
Autoři: MUDr. Jana Kubátová

Pokročilá Parkinsonova nemoc − úskalí a možnosti léčby
Autoři: doc. MUDr. Marek Baláž, Ph.D.

Léčba diabetes mellitus 2. typu pomocí GLP- 1 RA

Depresivní porucha a zánětlivé procesy
Autoři: MUDr. Juraj Tkáč

Methotrexát a jeho formy podávání v revmatologii
Autoři: MUDr. Liliana Šedová

Všechny kurzy
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se