SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

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):270–3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122–7.

Article  CAS  PubMed  Google Scholar 

Henry BM, Lippi G. Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus Disease 2019 (COVID-19): pooled analysis of early reports. J Crit Care. 2020;58:27–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Collaborators C-EM. Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020-21. Lancet. 2022;399(10334):1513–36.

Article  Google Scholar 

Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, Definition WCC. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):E102–E7.

Article  CAS  PubMed  Google Scholar 

Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mehandru S, Merad M. Pathological sequelae of long-haul COVID. Nat Immunol. 2022;23(2):194–202.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, et al. Persistent fatigue following SARS-CoV-2 Infection is common and Independent of severity of initial Infection. PLoS ONE. 2020;15(11):e0240784.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Files JK, Sarkar S, Fram TR, Boppana S, Sterrett S, Qin K et al. Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses. JCI Insight. 2021;6(15).

Phillips S, Williams MA. Confronting our Next National Health Disaster - Long-Haul Covid. N Engl J Med. 2021;385(7):577–9.

Article  CAS  PubMed  Google Scholar 

Priya SP, Sunil PM, Varma S, Brigi C, Isnadi M, Jayalal JA, et al. Direct, indirect, post-infection damages induced by coronavirus in the human body: an overview. Virusdisease. 2022;33(4):429–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Letarov AV, Babenko VV, Kulikov EE. Free SARS-CoV-2 spike protein S1 particles may play a role in the pathogenesis of COVID-19 Infection. Biochem (Mosc). 2021;86(3):257–61.

Article  CAS  Google Scholar 

Petrovszki D, Walter FR, Vigh JP, Kocsis A, Valkai S, Deli MA et al. Penetration of the SARS-CoV-2 spike protein across the blood-brain barrier, as revealed by a combination of a human cell culture Model System and Optical Biosensing. Biomedicines. 2022;10(1).

Oh J, Cho WH, Barcelon E, Kim KH, Hong J, Lee SJ. SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death. Sci Rep. 2022;12(1):5496.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Theoharides TC. Could SARS-CoV-2 spike protein be responsible for Long-COVID syndrome? Mol Neurobiol. 2022;59(3):1850–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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;181(2):271–80. e8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bollavaram K, Leeman TH, Lee MW, Kulkarni A, Upshaw SG, Yang J et al. Multiple sites on SARS-CoV-2 spike protein are susceptible to proteolysis by cathepsins B, K, L, S, and V. Protein Sci. 2021;30(6):1131-43.

Rhea EM, Logsdon AF, Hansen KM, Williams LM, Reed MJ, Baumann KK, et al. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat Neurosci. 2021;24(3):368–78.

Article  CAS  PubMed  Google Scholar 

Ogata AF, Maley AM, Wu C, Gilboa T, Norman M, Lazarovits R, et al. Ultra-sensitive serial profiling of SARS-CoV-2 antigens and antibodies in plasma to Understand Disease Progression in COVID-19 patients with severe Disease. Clin Chem. 2020;66(12):1562–72.

Article  PubMed  PubMed Central  Google Scholar 

Schultheiss C, Willscher E, Paschold L, Gottschick C, Klee B, Bosurgi L, et al. Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19. J Med Virol. 2023;95(1):e28364.

Article  CAS  PubMed  Google Scholar 

Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, et al. SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE 2. Circ Res. 2021;128(9):1323–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nuovo GJ, Magro C, Shaffer T, Awad H, Suster D, Mikhail S, et al. Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein. Ann Diagn Pathol. 2021;51:151682.

Article  PubMed  Google Scholar 

Perico L, Morigi M, Galbusera M, Pezzotta A, Gastoldi S, Imberti B, et al. SARS-CoV-2 spike protein 1 activates microvascular endothelial cells and complement system leading to platelet aggregation. Front Immunol. 2022;13:827146.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Avolio E, Carrabba M, Milligan R, Kavanagh Williamson M, Beltrami AP, Gupta K, et al. The SARS-CoV-2 spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular Disease. Clin Sci (Lond). 2021;135(24):2667–89.

Article  CAS  PubMed  Google Scholar 

Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis. 2020;146:105131.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lucero CM, Prieto-Villalobos J, Marambio-Ruiz L, Balmazabal J, Alvear TF, Vega M et al. Hypertensive Nephropathy: unveiling the possible involvement of Hemichannels and Pannexons. Int J Mol Sci. 2022;23(24).

Peng B, Xu C, Wang S, Zhang Y, Li W. The role of Connexin Hemichannels in Inflammatory Diseases. Biology (Basel). 2022;11(2).

Gonzalez-Jamett A, Vasquez W, Cifuentes-Riveros G, Martinez-Pando R, Saez JC, Cardenas AM. Oxidative stress, inflammation and Connexin Hemichannels in muscular dystrophies. Biomedicines. 2022;10(2).

Mugisho OO, Green CR. The NLRP3 inflammasome in age-related eye Disease: evidence-based connexin hemichannel therapeutics. Exp Eye Res. 2022;215:108911.

Article  CAS  PubMed  Google Scholar 

Retamal MA, Fernandez-Olivares A, Stehberg J. Over-activated hemichannels: a possible therapeutic target for human Diseases. Biochim Biophys Acta Mol Basis Dis. 2021;1867(11):166232.

Article  CAS  PubMed  Google Scholar 

Xing L, Yang T, Cui S, Chen G. Connexin Hemichannels in astrocytes: role in CNS disorders. Front Mol Neurosci. 2019;12:23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Syrjanen J, Michalski K, Kawate T, Furukawa H. On the molecular nature of large-pore channels. J Mol Biol. 2021;433(17):166994.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Saez JC, Leybaert L. Hunting for connexin hemichannels. FEBS Lett. 2014;588(8):1205–11.

Article  CAS  PubMed  Google Scholar 

Plotkin LI. Connexin 43 hemichannels and intracellular signaling in bone cells. Front Physiol. 2014;5:131.

Article  PubMed  PubMed Central  Google Scholar 

D’Hondt C, Iyyathurai J, Himpens B, Leybaert L, Bultynck G. Cx43-hemichannel function and regulation in physiology and pathophysiology: insights from the bovine corneal endothelial cell system and beyond. Front Physiol. 2014;5:348.

PubMed  PubMed Central  Google Scholar 

Retamal MA, Riquelme MA, Stehberg J, Alcayaga J. Connexin43 hemichannels in Satellite glial cells, can they influence sensory neuron activity? Front Mol Neurosci. 2017;10:374.

Article  PubMed  PubMed Central  Google Scholar 

Beyer EC, Berthoud VM. Connexin hemichannels in the lens. Front Physiol. 2014;5:20.

Article  PubMed  PubMed Central  Google Scholar 

Stout CE, Costantin JL, Naus CC, Charles AC. Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem. 2002;277(12):10482–8.

Article  CAS  PubMed  Google Scholar 

Turovsky EA, Varlamova EG, Turovskaya MV. Activation of Cx43 hemichannels induces the generation of ca(2+) oscillations in White adipocytes and Stimulates Lipolysis. Int J Mol Sci. 2021;22(15).

Khalil AA, Ilina O, Vasaturo A, Venhuizen JH, Vullings M, Venhuizen V et al. Collective invasion induced by an autocrine purinergic loop through connexin-43 hemichannels. J Cell Biol. 2020;219(10).

Recabal A, Fernandez P, Lopez S, Barahona MJ, Ordenes P, Palma A, et al. The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway. J Neurochem. 2021;156(2):182–99.

Article  CAS  PubMed  Google Scholar 

De Smet MA, Lissoni A, Nezlobinsky T, Wang N, Dries E, Perez-Hernandez M et al. Cx43 hemichannel microdomain sig

Comments (0)

No login
gif