Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
from 01.01.2023 until now
Kirov Military Medical Academy
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Haloperidol (butyrophenone derivative) and phenothiazine derivatives chlorpromazine and trifluoperazine belong to the typical first-generation neuroleptics and are widely used in clinical practice for treatment of schizophrenia and other mental diseases. Their multifaceted effect on cellular processes is well known. Thus, a high affinity of typical neuroleptics for sigma-1 receptors was revealed. Sigma-1 receptors are ubiquitous multifunctional ligand-operated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Acting as chaperones, sigma-1 receptors modulate a wide range of cellular processes in health and disease, including Ca2+ signaling processes. To elucidate the involvement of sigma-1 receptors in Ca2+ signaling processes in macrophages, the effect of sigma-1 receptor ligands on Ca2+ responses induced by disulfide-containing immunomodulators glutoxim and molixan in rat peritoneal macrophages was investigated. Using Fura-2AM microfluorimetry we have shown that haloperidol, chlorpromazine and trifluoperazine significantly suppress both Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by glutoxim or molixan in peritoneal macrophages. The data obtained indicate the possible involvement of sigma-1 receptors in the complex signaling cascade triggered by glutoxim or molixan and leading to intracellular Ca2+ concentration increase in macrophages. The results also suggest the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.
neuroleptics, sigma-1 receptors, intracellular Ca2+ concentration, macrophages
1. Dilsaver S.C. Antipsychotic agents: a review. Amer. Fam. Phys., 1993, vol. 47, pp. 199-204.
2. Ayano G. First generation antipsychotics: pharmacokinetics, pharmacodynamics, therapeutic effects and side effects: A review. Res. Rev. J. Chem., 2016, vol. 5, pp. 53-63.
3. Tam S.W., Cook L. Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes. Proc. Natl. Acad. Sci. USA, 1984, vol. 81, pp. 5618-5621.
4. Su T.-P., Hayashi T., Maurice T., Buch S., Ruoho A.E. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol. Sci., 2010, vol. 31, pp. 557-566.
5. Su T.-P., Su T.-C., Nakamura Y., Tsai S.-Y. The sigma-1 receptor as a pluripotent modulator in living systems. Trends Pharmacol. Sci., 2016, vol. 37, no. 4, pp. 262-278.
6. Rousseaux C.G., Greene S.F. Sigma receptors [σRs]: Biology in normal and diseased states. J. Recept. Signal Transduct. Res., 2016, vol. 36, no. 4, pp. 327-388.
7. Schmidt H.R., Kruse A.C. The molecular function of σ receptors: past, present, and future. Trends Pharmacol. Sci., 2019, vol. 40, no. 9, pp. 636-654.
8. Aishwarya R., Abdullah C.S., Morshed M., Remex N.S., Bhuiyan M.S. Sigmar1’s molecular, cellular, and biological functions in regulating cellular pathophysiology. Front. Physiol., 2021, vol. 12, doi: https://doi.org/10.3389/fphys.2021.705575.
9. Penke B., Fulop L., Szucs M., Frecska E. The role of sigma-1 receptor, an intracellular chaperone in neurodegenerative diseases. Curr. Neuropharmacol., 2018, vol. 16, pp. 97-116.
10. Cobos E.J., Entrena J.M., Nieto F.R., Cendan C.M., Del Pozo E. Pharmacology and therapeutic potential of sigma (1) receptor ligands. Curr. Neuropharmacol., 2008, vol. 6, no. 4, pp. 344-366.
11. Maurice T., Su T.-P. The pharmacology of sigma-1 receptors. Pharmacol. Ther., 2009, vol. 124, no. 2, pp. 195-206.
12. Chu U.B., Ruoho A.E. Biochemical pharmacology of the sigma-1 receptor. Mol. Pharmacol., 2016, vol. 89, pp. 142-153.
13. Pontisso I., Combettes L. Role of sigma-1 receptor in calcium modulation: possible involvement in cancer. Genes, 2021, vol. 12, no. 2, p. 139, doi:https://doi.org/10.3390/genes12020139.
14. Hayashi T., Su T.-P. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell, 2007, vol. 131, pp. 596-610.
15. Srivats S., Balasuriya D., Pasche M., Vistal G., Edwardson J. M., Taylor C.W., Murrell-Lagnado R.D. Sigma 1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1. J. Cell Biol., 2016, vol. 213, no. 1, pp. 65-79.
16. Hayashi T., Maurice T., Su T.-P. Ca2+ signalling via σ1-receptors: novel regulatory mechanism affecting intracellular Ca2+ concentration. J. Pharmacol. Exper. Ther., 2000, vol. 293, pp. 788-798.
17. Monnet F.P. Sigma-1 receptor as regulator of neuronal intracellular Ca2+: clinical and therapeutic relevance. Biol. Cell., 2005, vol. 97, pp. 878-883.
18. Brailoiu G.C., Deliu E., Console-Bram L.M., Soboloff J., Abood M.E., Unterwald E.M., Brailoiu E. Cocaine inhibits store-operated Ca2+ entry in brain microvascular endothelial cells: Critical role for sigma-1 receptors. Biochem. J., 2016, vol. 473, pp. 1-5.
19. Berlansky S., Humer C., Sallinger M., Frischauf I. More than just simple interaction between STIM and Orai proteins: CRAC channel function enabled by a network of interactions with regulatory proteins. Int. J. Mol. Sci., 2021, vol. 22, p. 471, doi:https://doi.org/10.3390/ijms22010471.
20. Borisov A.E., Kozhemyakin L.A., Antushevich A.E., Ketliskaya O.S., Kashchenko V.A., Chepur S.V., Katsalucha V.V., Vasyukova E.L., Novichenkov A.O., Motushchuk I.E. Clinical and experimental grounds of the regional and systemic administration of the thiopoetin group medicines for cirrhosis of the liver. Vestnic hirurgii im. I.I. Grekova, 2001, vol. 4, no. 2, pp. 32-38. (In Russ.)
21. Sokolova G.B., Sinitsyn M.V., Kozhemiakin L.A., Perel'man M.I. Glutoxim in the complex treatment of tuberculosis. Antibiot. Khimioter., 2002, vol. 2, pp. 20-23. (In Russ.)
22. Antushevich A.A., Antonov V.G., Grebenyuk A.N., Antushevich A.E., Ladanova T.V., Burova E.B. Pathophysiologic rationale of effectiveness of glutoxim supportive therapy add-on to radiotherapy management of oropharyngeal cancer. Vestnik Rossiiskoi Voenno-medicinskoi akademii., 2013, vol. 3, no. 43, pp. 32-37. (In Russ.)
23. Tolstoy O.A., Tsygan V.N., Klimov A.G., Stepanov A.V., Antushevich A.E. Experimental evaluation of the efficiency of the drug molixan on restoring the operation of virus-infected laboratory animals. Bull. Russ. Military Med. Acad., 2019, vol. 38, no. 1, pp. 271-277. (In Russ.)
24. Dubina M.V., Gomonova V.V., Taraskina A.E., Vasilyeva N.V., Sayganov S.A. Pathogenesis-based pre-exposure prophylaxis associated with low risk of SARS-CoV-2 infection in healthcare workers at a designated COVID-19 hospital, 2020, doi:https://doi.org/10.1101/2020.09.25.20199562.
25. Kurilova L.S., Krutetskaya Z.I., Lebedev O.E., Krutetskaya N.I., Antonov V.G. The effect of oxidized glutathione and its pharmacological analogue glutoxim on intracellular Ca2+ concentration in macrophages. Cell Tiss. Biol., 2008, vol. 2, no. 3, pp. 322-332. (In Russ.)
26. Kurilova L.S., Krutetskaya Z.I., Lebedev O.E., Krutetskaya N.I., Antonov V.G. The effect of drug molixan on Ca2+ signaling processes in macrophages. Tsitologiya, 2011, vol. 53, p. 708. (In Russ.)
27. Whittemore E.R., Ilyin V.I., Woodward R.M. Antagonism of N-methyl-D-aspartate receptors by σ site ligands: potency, subtype-selectivity and mechanisms of inhibition. J. Pharmacol. Exp. Therapeut., 1997, vol. 282, pp. 326-338.
28. Cobos E.J., Del Pozo E., Baeyens J.M. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells. J. Neurochem., 2007, vol. 102, pp. 812-825.
29. Itzhak Y., Ruhland M., Krahling H. Binding of umespirone to the sigma receptor: evidence for multiple affinity states. Neuropharmacol., 1990, vol. 29, pp. 181-184.
30. Hayashi T., Su T.-P. Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs., 2004, vol. 18, no. 5, pp. 269-284.
31. Schuster D.I., Arnold F.J., Murphy R.B. Purification, pharmacological characterization and photoaffinity labeling of sigma receptors from rat and bovine brain. Brain Res., 1995, vol. 670, pp. 14-28.
32. Hanner M., Moebius F.F., Flandorfer A., Knaus H.G., Striessnig J., Kempner E., Glossman H. Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc. Natl. Acad. Sci. USA, 1996, vol. 93, pp. 8072-8077.
33. Conrad R.E. Induction and collection of peritoneal exudate macrophages. In: Manual of macrophages methodology. N.-Y.: Marcell Dekker, 1981, pp. 5-11.
34. Randriamampita C., Trautmann A. Ionic channels in murine macrophages. Cell. Biol., 1987, vol. 105, pp. 761-769.
35. Monahan R.A., Dvorak H.F., Dvorak A.M. Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages and lymphocytes. Blood, 1981, vol. 58, pp. 1089-1099.
36. Bruce J.I.E., Elliott A.C. Pharmacological evaluation of the role of cytochrome P450 in intracellular calcium signaling in rat pancreatic acinar cells. Brit. J. Physiol., 2000, vol. 131, pp. 761-771.
37. Xie Q., Zhang Y., Zhai C., Bonanno J.A. Calcium influx factor from cytochrome P-450 metabolism and secretion-like coupling mechanisms for capacitative calcium entry in corneal endothelial cells. J. Biol. Chem., 2002, vol. 277, pp. 16559-16566, doi:https://doi.org/10.1074/jbc.M109518200.
38. Grynkiewicz G., Poenie M., Tsien R.Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 1985, vol. 260, pp. 3440-3450.
39. Krutetskaya Z.I., Milenina L.S., Naumova A.A., Butov S.N., Antonov V.G., Nozdrachev A.D. Sigma-1 receptor antagonist haloperidol attenuates store-dependent Ca2+ entry in macrophages. Doklady Biochem. Biophys., 2018, vol. 480, no. 1, pp. 162-165. (In Russ.)
40. Harper J.L., Shin Y., Daly J.W. Loperamide: A positive modulator for store-operated calcium channels? Proc. Natl. Acad. Sci. USA., 1997, vol. 94, pp. 14912-14917.
41. Harper J.L., Daly J.W. Inhibitors of store-operated calcium channels: Imidazoles, phenothiazines, and other tricyclics. Drug Dev. Res., 1999, vol. 47, pp. 107-117.
42. Choi S.-Y., Kim Y.-H., Lee Y.-K., Kim K.-T. Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells. British J. Pharmacol., 2001, vol. 132, pp. 411-418.
43. Wang L., Zhang L., Li S., Zheng Y., Yan X., Chen M., Wang H., Putney J.W., Luo D. Retrograde regulation of STIM1-Orai1 interaction and store-operated Ca2+ entry by calsequestrin. Sci. Rep., 2015, vol. 5, pp. 1-12.
44. Amer M.S., McKeown L., Tumova S., Liu R., AL Seymour V., Wilson L.A., Naylor J., Greenhalgh K., Hou B., Majeed Y., Turner P., Sedo A., O'Regan D. J., Li J., Bon R.S., Porter K.E., Beech D.J. Inhibition of endothelial cell Ca2+ entry and transient receptor potential channels by sigma-1 receptor ligands. Br. J. Pharmacol., 2013, vol. 168, pp. 1445-1455.
45. Gasparre G., Abate C., Carlucci R., Berardi F., Cassano G. The σ1 receptor agonist (+)-pentazocine increases store-operated Ca2+ entry in MCF7σ1 and SK-N-SH cell lines. Pharmacol. Rep., 2017, vol. 69, pp. 542-545.
46. Ogata N., Yoshii M., Narahashi T. Differential block of sodium and calcium channels by chlorpromazine in mouse neuroblastoma cells. J. Physiol., 1990, vol. 420, pp. 165-183.
47. Ogata N., Narahashi T. Potent blocking action of chlorpromazine on two types of calcium channels in cultured neuroblastoma cells. J. Pharmacol. Exp. Ther., 1990, vol. 252, no. 3, pp. 1142-1149.
48. McNaughton N.C.L., Green P.J., Randall A.D. Inhibition of human α1E subunit-mediated Ca2+ channels by the antipsychotic agent chlorpromazine. Acta Physiol. Scand., 2001, vol. 173, pp. 401-408.
49. Ito K., Nakazawa K., Koizumi S., Liu M., Takeuchi K., Hashimoto T., Ohno Y., Inoue K. Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells. Eur. J. Pharmacol., 1996, vol. 314, no. 1-2, pp. 143-150.
50. Nakazawa K., Higo K., Abe K., Tanaka Y., Saito H., Matsuki N. Blockade by calmodulin inhibitors of Ca2+ channels in smooth muscle from rat vas deferens. Br. J. Pharmacol., 1993, vol. 109, pp. 137-141.
51. Cruzblanca H., Gamino S.M., Bernal J., Alvarez-Leefmans F.J. Trifluoperazine enhancement of Ca2+-dependent inactivation of L-type Ca2+ currents in Helix aspersa neurons. Invert. Neurosci., 1998, vol. 3, no. 4, pp. 269-278.
52. Flaim S.F., Brannan M.D., Swioart S.C., Gleason M.M., Muschek L.D. Neuroleptic drugs attenuate calcium influx and tension development in rabbit thoracic aorta: Effects of pimozide, penfluridol, chlorpromazine, and haloperidol. Proc. Natl. Acad. Sci. USA., 1985, vol. 82, pp. 1237-1241.
53. Church J., Fletcher E.J. Blockade by sigma site ligands of high voltage-activated Ca2+channels in rat and mouse cultured hippocampal pyramidal neurones. Brit. J. Pharmacol., 1995, vol. 116, pp. 2801-2810.
54. Tarabova B., Novakova M., Lacinova L. Haloperidol moderately inhibits cardiovascular L-type calcium current. Gen. Physiol. Biophys., 2009, vol. 28, pp. 249-259.
55. Zhang H., Cuevas J. Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons. J. Neurophysiol., 2002, vol. 87, pp. 2867-2879.
56. Santi C.M., Cayabyab F.S., Sutton K.G., McRory J.E., Mezeyova J., Hamming K.S., Parker D., Stea A., Snutch T.P. Differential inhibition of T-type calcium channels by neuroleptics. J. Neurosci., 2002, vol. 22, no. 2, pp. 396-403.
57. Tsai S-Y., Hayashi T., Mori T., Su T-P. Sigma-1 receptor chaperones and diseases. Cent. Nerv. Syst. Agents Med. Chem., 2009, vol. 9, no. 3, pp. 184-189.
58. Tsai S-Y., Pokrass M.J., Klauer N.R., De Credico N.E., Su T-P. Sigma-1 receptor chaperones in neurodegenerative and psychiatric disorders. Expert Opin. Ther. Targets., 2014, vol. 18, no. 12, pp. 1461-1476.
59. Ishikawa M., Hashimoto K. The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases. J. Receptor, Ligand Channel Res., 2010, vol. 3, pp. 25-36.
60. Hayashi T. Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs. J. Pharmacol. Sci., 2015, vol. 127, no. 1, pp. 2-5.
61. Voronin M.V., Vakhitova Y.V., Seredenin S.B. Chaperone Sigma1R and antidepressant effect. Int. J. Mol. Sci., 2020, vol. 21, no. 19, doi:https://doi.org/10.3390/ijms21197088.
62. Ryskamp D., Wu J., Geva M., Kusko R., Grossman I., Hayden M., Bezprozvanny I. The sigma 1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease. Neurobiol. Dis., 2017, vol. 97, pp. 46-59.
63. Ryskamp D.A., Korban S., Zhemkov V., Kraskovskaya N., Bezprozvanny I. Neuronal sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases. Front. Neurosci., 2019, vol. 13, 862, doi:https://doi.org/10.3389/fnins.2019.00862.
64. Yang K., Wang C., Sun T. The roles of intracellular chaperone proteins, sigma receptors, in Parkinson’s disease (PD) and major depressive disorder (MDD). Front. Pharmacol., 2019, vol. 10, doi:https://doi.org/10.3389/fphar.2019.00528.
65. Herrando-Grabulosa M., Gaja-Capdevila N., Vela J.M., Navarro X. Sigma 1 receptor as a therapeutic target for amyotrophic lateral sclerosis. Br. J. Pharmacol., 2020, vol. 178, no. 6, pp. 1336-1352.
66. Kim F.J., Maher C.M. Sigma1 pharmacology in the context of cancer. Handb. Exp. Pharmacol., 2017, vol. 244, pp. 237-308.
67. Merlos M., Burgueño J., Portillo-Salido E., Plata-Salaman C.R., Vela J.M. Pharmacological modulation of the sigma 1 receptor and the treatment of pain. Adv. Exp. Med. Biol., 2017, vol. 964, pp. 85-107.
68. Smith S.B., Wang J., Cui X., Mysona B.A., Zhao J., Bollinger K.E. Sigma 1 receptor: a novel therapeutic target in retinal disease. Prog. Retin Eye Res., 2018, vol. 67, pp. 130-149.
69. Vela J.M. Repurposing sigma-1 receptor ligands for COVID-19 therapy? Front. Pharmacol., 2020, vol. 11, doi:https://doi.org/10.3389/fphar.2020.582310.
70. Hashimoto K. Repurposing of CNS drugs to treat COVID-19 infection: Targeting the sigma-1 receptor. Eur. Arch. Psychiatry Clin. Neurosci., 2021, vol. 271, no. 2, pp. 249-258.
71. Plaze M., Attali D., Petit A.-C., Blatzer M., Simon-Loriere E., Vinckier F., Cachia A., Chretien F., Gaillard R. Repurposing chlorpromazine to treat COVID-19: The reCoVery study. L’Encephale., 2020, vol. 46, no. 3, pp. 169-172.
72. Muric N.N., Arsenijevic N.N., Milica M., Borovcanin M.M. Chlorpromazine as a potential antipsychotic choice in COVID-19 treatment. Front. Psychiatry, 2020, vol. 11, doi:https://doi.org/10.3389/fpsyt.2020.612347.
73. Nobile B., Durand M., Courtet P., Van de Perre P., Nagot N., Moles J.P., Olie E. Could the antipsychotic chlorpromazine be a potential treatment for SARS-CoV-2? Schizophrenia Res., 2020, vol. 223, pp. 373-375.
74. Stip E. Psychiatry and COVID-19: The role of chlorpromazine. Can. J. Psychiatry, 2020, vol. 65, no. 10, pp. 739-740.
75. Stip E., Rizvi T.A., Mustafa F., Javaid S., Aburuz S., Ahmed N.N., Abdel Aziz K., Arnone D., Subbarayan A., Al Mugaddam F., Khan G. The large action of chlorpromazine: translational and transdisciplinary considerations in the face of COVID-19. Front. Pharmacol., 2020, vol. 11, doi:https://doi.org/10.3389/fphar.2020.577678.
76. Otręba M., Korsmider L., Rzepecka-Stojko A. Antiviral activity of chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine towards RNA-viruses. A review. Europ. J. Pharmacol., 2020, vol. 887, doi:https://doi.org/10.1016/j.ejphar.2020.173553.
77. Gitahy Falcao Faria C., Weiner L., Petrignet J., Hingray C., Ruiz De Pellon Santamaria A., Villoutreix B.O., Beaune P., Leboyer M., Javelot H. Antihistamine and cationic amphiphilic drugs, old molecules as new tools against the COVID-19? Med. Hypotheses., 2021, vol. 148, doi:https://doi.org/10.1016/j.mehy.2021.110508.
78. Plaze M., Attali D., Prot M., Petit A.-C., Blatzer M., Vinckier F., Levillayer L., Chiaravalli J., Perin-Dureau F., Cachia A., Friedlander G., Chretien F., Simon-Loriere E., Gaillard R. Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine. Int. J. Antimicrobial Agents., 2021, vol. 57, no. 3, doi:https://doi.org/10.1016/j.ijantimicag.2020.106274.
79. Hoertel N., Sanchez-Rico M., Vernet R., Jannot A-S., Neuraz A., Blanco C., Lemogne C., Airagnes G., Paris N., Daniel Ch., Gramfort A., Lemaitre G., Bernaux M., Bellamine A., Beeker N., Limosin F. Observational study of haloperidol in hospitalized patients with COVID-19. PLoS One, 2021, vol. 16, no. 2, e0247122, doi:https://doi.org/10.1371/journal. pone.0247122.
80. Hoertel N., Sanchez-Rico M.,·Vernet R., Jannot A-S., Neuraz A.,·Blanco C., Lemogne C., Airagnes G., Paris N., Daniel Ch., Gramfort A., Lemaitre G., Bernaux M., Bellamine A., Beeker N. Observational study of chlorpromazine in hospitalized patients with COVID-19. Clin. Drug Investigation, 2021, vol. 41, no. 3, pp. 221-233.
81. Zhoua Y., Freyb T.K., Yanga J.J. Viral calciomics: interplays between Ca2+ and virus. Cell Calcium, 2009, vol. 46, no. 1, pp. 1-17.
82. Chen X., Cao R., Zhong W. Host calcium channels and pumps in viral infections. Cells, 2019, vol. 9, iss. 1, 94, doi:https://doi.org/10.3390/cells9010094.
83. Solaimanzadeh I. Nifedipine and amlodipine are associated with improved mortality and decreased risk for intubation and mechanical ventilation in elderly patients hospitalized for COVID-19. Cureus, 2020, vol. 12, no. 5, e8069, doi:https://doi.org/10.7759/cureus.8069.
84. Zhang L.-K., Sun Y., Zeng H., Wang Q., Jiang X., Shang W-J., Wu Y., Li Sh., Zhang Y-L., Hao Z.-N., Chen H., Jin R., Liu W., Li H., Peng K., Xiao G. Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension. Cell Discovery, 2020, vol. 6, no. 1, art. no. 96, doi:https://doi.org/10.1038/s41421-020-00235-0.
85. Miller J., Bruen C., Schnaus M., Zhang J., Ali S., Lind A., Stoecker Z., Stauderman K., Hebbar S. Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: Results from a randomized controlled trial. Crit. Care, 2020, vol. 24, art. no. 502, doi:https://doi.org/10.1186/s13054-020-03220-x.
86. Berlansky S., Sallinger M., Grabmayr H., Humer C., Bernhard A., Fahrner M., Frischauf I. Calcium signals during SARS-CoV-2 infection: Assessing the potential of emerging therapies. Cells, 2022, vol. 11, art. no. 253, doi:https://doi.org/10.3390/cells11020253.
