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08-08-2022 | Smelling Disorder | Review

Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2

Authors: Ali Karimian, Mohaddeseh Behjati, Mohammad Karimian

Published in: Archives of Virology | Issue 10/2022

Abstract

Since 2020, SARS-CoV-2 has caused a pandemic virus that has posed many challenges worldwide. Infection with this virus can result in a number of symptoms, one of which is anosmia. Olfactory dysfunction can be a temporary or long-term viral complication caused by a disorder of the olfactory neuroepithelium. Processes such as inflammation, apoptosis, and neuronal damage are involved in the development of SARS-CoV-2-induced anosmia. One of the receptors that play a key role in the entry of SARS-CoV-2 into the host cell is the transmembrane serine protease TMPRSS2, which facilitates this process by cleaving the viral S protein. The gene encoding TMPRSS2 is located on chromosome 21. It contains 15 exons and has many genetic variations, some of which increase the risk of disease. Delta strains have been shown to be more dependent on TMPRSS2 for cell entry than Omicron strains. Blockade of this receptor by serine protease inhibitors such as camostat and nafamostat can be helpful for treating SARS-CoV-2 symptoms, including anosmia. Proper understanding of the different functional aspects of this serine protease can help to overcome the therapeutic challenges of SARS-CoV-2 symptoms, including anosmia. In this review, we describe the cellular and molecular events involved in anosmia induced by SARS-CoV-2 with a focus on the function of the TMPRSS2 receptor.

Veronese S, Sbarbati A (2021) Chemosensory systems in COVID-19: evolution of scientific research. ACS Chem Neurosci 12(5):813–824. https://doi.org/10.1021/acschemneuro.0c00788CrossRefPubMed

Cooper KW, Brann DH, Farruggia MC, Bhutani S, Pellegrino R, Tsukahara T et al (2020) COVID-19 and the chemical senses: supporting players take center stage. Neuron 107(2):219–233. https://doi.org/10.1016/j.neuron.2020.06.032CrossRefPubMedPubMedCentral

Hoang MP, Kanjanaumporn J, Aeumjaturapat S, Chusakul S, Seresirikachorn K, Snidvongs K (2020) Olfactory and gustatory dysfunctions in COVID-19 patients: a systematic review and meta-analysis. Asian Pac J Allergy Immunol 38(3):162–169. https://doi.org/10.12932/ap-210520-0853CrossRefPubMed

Lee Y, Min P, Lee S, Kim SW (2020) Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J Korean Med Sci 35(18):e174. https://doi.org/10.3346/jkms.2020.35.e174CrossRefPubMedPubMedCentral

Han AY, Mukdad L, Long JL, Lopez IA (2020) Anosmia in COVID-19: mechanisms and significance. Chem Senses. https://doi.org/10.1093/chemse/bjaa040CrossRefPubMed

Butowt R, von Bartheld CS (2021) Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist 27(6):582–603. https://doi.org/10.1177/1073858420956905CrossRefPubMedPubMedCentral

Eliezer M, Hautefort C, Hamel AL, Verillaud B, Herman P, Houdart E et al (2020) Sudden and complete olfactory loss of function as a possible symptom of COVID-19. JAMA Otolaryngol Head Neck Surg 146(7):674–675. https://doi.org/10.1001/jamaoto.2020.0832CrossRefPubMed

Printza A, Constantinidis J (2020) The role of self-reported smell and taste disorders in suspected COVID-19. Eur Arch Oto-rhino-laryngol 277(9):2625–2630. https://doi.org/10.1007/s00405-020-06069-6CrossRef

Vaira LA, Salzano G, Deiana G, De Riu G (2020) Anosmia and ageusia: common findings in COVID-19 patients. Laryngoscope 130(7):1787. https://doi.org/10.1002/lary.28692CrossRefPubMedPubMedCentral

10.

Baig AM, Khaleeq A, Ali U, Syeda H (2020) Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 11(7):995–998. https://doi.org/10.1021/acschemneuro.0c00122CrossRefPubMed

11.

Brann JH, Firestein SJ (2014) A lifetime of neurogenesis in the olfactory system. Front Neurosci 8:182. https://doi.org/10.3389/fnins.2014.00182CrossRefPubMedPubMedCentral

12.

Sedaghat AR, Gengler I, Speth MM (2020) Olfactory dysfunction: a highly prevalent symptom of COVID-19 with public health significance. Otolaryngology Head Neck Surg 163(1):12–15. https://doi.org/10.1177/0194599820926464CrossRef

13.

Bryche B, St Albin A, Murri S, Lacôte S, Pulido C, Ar Gouilh M et al (2020) Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun 89:579–586. https://doi.org/10.1016/j.bbi.2020.06.032CrossRefPubMedPubMedCentral

14.

Aragão M, Leal MC, Cartaxo Filho OQ, Fonseca TM, Valença MM (2020) Anosmia in COVID-19 associated with injury to the olfactory bulbs evident on MRI. AJNR Am J Neuroradiol 41(9):1703–1706. https://doi.org/10.3174/ajnr.A6675CrossRefPubMedPubMedCentral

15.

Politi LS, Salsano E, Grimaldi M (2020) Magnetic resonance imaging alteration of the brain in a patient with Coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol 77(8):1028–1029. https://doi.org/10.1001/jamaneurol.2020.2125CrossRefPubMed

16.

Wang L, Shen Y, Li M, Chuang H, Ye Y, Zhao H et al (2020) Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Neurol 267(10):2777–2789. https://doi.org/10.1007/s00415-020-09974-2CrossRefPubMedPubMedCentral

17.

Bao L, Deng W, Huang B, Gao H, Liu J, Ren L et al (2020) The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 583(7818):830–833. https://doi.org/10.1038/s41586-020-2312-yCrossRefPubMed

18.

Bilinska K, Jakubowska P, Von Bartheld CS, Butowt R (2020) Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age. ACS Chem Neurosci 11(11):1555–1562. https://doi.org/10.1021/acschemneuro.0c00210CrossRefPubMed

19.

Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B et al (2020) Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. https://doi.org/10.1126/sciadv.abc5801CrossRefPubMed

20.

Chen J, Subbarao K (2007) The Immunobiology of SARS*. Annu Rev Immunol 25:443–472. https://doi.org/10.1146/annurev.immunol.25.022106.141706CrossRefPubMed

21.

Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T (2011) A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol 85(2):873–882. https://doi.org/10.1128/jvi.02062-10CrossRefPubMed

22.

Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S (2009) The spike protein of SARS-CoV–a target for vaccine and therapeutic development. Nat Rev Microbiol 7(3):226–236. https://doi.org/10.1038/nrmicro2090CrossRefPubMedPubMedCentral

23.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2):271–80.e8. https://doi.org/10.1016/j.cell.2020.02.052CrossRefPubMedPubMedCentral

24.

Kanageswaran N, Demond M, Nagel M, Schreiner BS, Baumgart S, Scholz P et al (2015) Deep sequencing of the murine olfactory receptor neuron transcriptome. PLoS ONE 10(1):e0113170. https://doi.org/10.1371/journal.pone.0113170CrossRefPubMedPubMedCentral

25.

Saraiva LR, Ibarra-Soria X, Khan M, Omura M, Scialdone A, Mombaerts P et al (2015) Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. Sci Rep 5:18178. https://doi.org/10.1038/srep18178CrossRefPubMedPubMedCentral

26.

Olender T, Keydar I, Pinto JM, Tatarskyy P, Alkelai A, Chien MS et al (2016) The human olfactory transcriptome. BMC Genom 17(1):619. https://doi.org/10.1186/s12864-016-2960-3CrossRef

27.

Nickell MD, Breheny P, Stromberg AJ, McClintock TS (2012) Genomics of mature and immature olfactory sensory neurons. J Comp Neurol 520(12):2608–2629. https://doi.org/10.1002/cne.23052CrossRefPubMedPubMedCentral

28.

Durante MA, Kurtenbach S, Sargi ZB, Harbour JW, Choi R, Kurtenbach S et al (2020) Single-cell analysis of olfactory neurogenesis and differentiation in adult humans. Nat Neurosci 23(3):323–326. https://doi.org/10.1038/s41593-020-0587-9CrossRefPubMedPubMedCentral

29.

McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C (2020) Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res 157:104859. https://doi.org/10.1016/j.phrs.2020.104859CrossRefPubMedPubMedCentral

30.

Chupp G, Spichler-Moffarah A, Søgaard OS, Esserman D, Dziura J, Danzig L et al (2022) A phase 2 randomized, double-blind, placebo-controlled trial of oral camostat mesylate for early treatment of COVID-19 outpatients showed shorter illness course and attenuation of loss of smell and taste. medRxiv. https://doi.org/10.1101/2022.01.28.22270035CrossRefPubMedPubMedCentral

31.

Koyama S, Ueha R, Kondo K (2021) Loss of smell and taste in patients with suspected COVID-19: analyses of patients’ reports on social media. J Med Internet Res 23(4):e26459. https://doi.org/10.2196/26459CrossRefPubMedPubMedCentral

32.

Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C et al (2020) Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA 323(20):2089–2090. https://doi.org/10.1001/jama.2020.6771CrossRefPubMedPubMedCentral

33.

Desai M, Oppenheimer J (2021) The importance of considering olfactory dysfunction during the COVID-19 pandemic and in clinical practice. J Allergy Clin Immunol Pract 9(1):7–12. https://doi.org/10.1016/j.jaip.2020.10.036CrossRefPubMed

34.

Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M et al (2020) SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 26(5):681–687. https://doi.org/10.1038/s41591-020-0868-6CrossRefPubMedPubMedCentral

35.

Rebholz H, Pfaffeneder-Mantai F, Knoll W, Hassel AW, Frank W, Kleber C (2021) Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence. Am J Otolaryngol 42(5):103014. https://doi.org/10.1016/j.amjoto.2021.103014CrossRefPubMedPubMedCentral

36.

Whitcroft KL, Hummel T (2020) Olfactory dysfunction in COVID-19: diagnosis and management. JAMA 323(24):2512–2514. https://doi.org/10.1001/jama.2020.8391CrossRefPubMed

37.

Sayin I, Yazici ZM (2020) Taste and smell impairment in SARS-CoV-2 recovers early and spontaneously: experimental data strongly linked to clinical data. ACS Chem Neurosci 11(14):2031–2033. https://doi.org/10.1021/acschemneuro.0c00296CrossRefPubMed

38.

Torabi A, Mohammadbagheri E, Akbari Dilmaghani N, Bayat AH, Fathi M, Vakili K et al (2020) Proinflammatory cytokines in the olfactory mucosa result in COVID-19 induced anosmia. ACS Chem Neurosci 11(13):1909–1913. https://doi.org/10.1021/acschemneuro.0c00249CrossRefPubMed

39.

Dushianthan A, Clark H, Madsen J, Mogg R, Matthews L, Berry L et al (2020) Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): a structured summary of a study protocol for a randomized controlled trial. Trials 21(1):1014. https://doi.org/10.1186/s13063-020-04944-5CrossRefPubMedPubMedCentral

40.

Lane AP, Turner J, May L, Reed R (2010) A genetic model of chronic rhinosinusitis-associated olfactory inflammation reveals reversible functional impairment and dramatic neuroepithelial reorganization. J Neurosci 30(6):2324–2329. https://doi.org/10.1523/jneurosci.4507-09.2010CrossRefPubMedPubMedCentral

41.

Goncalves S, Goldstein BJ (2016) Pathophysiology of olfactory disorders and potential treatment strategies. Curr Otorhinolaryngol Rep 4(2):115–121. https://doi.org/10.1007/s40136-016-0113-5CrossRefPubMedPubMedCentral

42.

Kollias G, Douni E, Kassiotis G, Kontoyiannis D (1999) On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Immunol Rev 169:175–194. https://doi.org/10.1111/j.1600-065x.1999.tb01315.xCrossRefPubMed

43.

Sandborn WJ, Hanauer SB (1999) Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety. Inflamm Bowel Dis 5(2):119–133. https://doi.org/10.1097/00054725-199905000-00008CrossRefPubMed

44.

Suzuki Y, Farbman AI (2000) Tumor necrosis factor-alpha-induced apoptosis in olfactory epithelium in vitro: possible roles of caspase 1 (ICE), caspase 2 (ICH-1), and caspase 3 (CPP32). Exp Neurol 165(1):35–45. https://doi.org/10.1006/exnr.2000.7465CrossRefPubMed

45.

Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I et al (2020) Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents 34(2):327–331. https://doi.org/10.23812/conti-eCrossRefPubMed

46.

Soler ZM, Patel ZM, Turner JH, Holbrook EH (2020) A primer on viral-associated olfactory loss in the era of COVID-19. Int Forum Allergy Rhinol 10(7):814–820. https://doi.org/10.1002/alr.22578CrossRefPubMedPubMedCentral

47.

Vaira LA, Salzano G, De Riu G (2020) The importance of olfactory and gustatory disorders as early symptoms of coronavirus disease (COVID-19). Br J Oral Maxillofac Surg 58(5):615–616. https://doi.org/10.1016/j.bjoms.2020.04.024CrossRefPubMedPubMedCentral

48.

Lechien JR, Hopkins C, Saussez S (2020) Sniffing out the evidence; It’s now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance. Rhinology 58(4):402–403. https://doi.org/10.4193/Rhin20.159CrossRefPubMed

49.

Gilani S, Roditi R, Naraghi M (2020) COVID-19 and anosmia in Tehran, Iran. Med Hypotheses 141:109757. https://doi.org/10.1016/j.mehy.2020.109757CrossRefPubMedPubMedCentral

50.

Imam SA, Lao WP, Reddy P, Nguyen SA, Schlosser RJ (2020) Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD? World J Otorhinolaryngol - Head Neck Surg 6(Suppl 1):S26-s32. https://doi.org/10.1016/j.wjorl.2020.05.004CrossRefPubMedPubMedCentral

51.

van Riel D, Verdijk R, Kuiken T (2015) The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system. J Pathol 235(2):277–287. https://doi.org/10.1002/path.4461CrossRefPubMed

52.

Najafloo R, Majidi J, Asghari A, Aleemardani M, Kamrava SK, Simorgh S et al (2021) Mechanism of anosmia caused by symptoms of COVID-19 and emerging treatments. ACS Chem Neurosci 12(20):3795–3805. https://doi.org/10.1021/acschemneuro.1c00477CrossRefPubMed

53.

Levine B (2002) Apoptosis in viral infections of neurons: a protective or pathologic host response? Curr Top Microbiol Immunol 265:95–118. https://doi.org/10.1007/978-3-662-09525-6_5CrossRefPubMed

54.

Mori I (2015) Transolfactory neuroinvasion by viruses threatens the human brain. Acta Virol 59(4):338–349. https://doi.org/10.4149/av_2015_04_338CrossRefPubMed

55.

Le Bon SD, Horoi M (2020) Is anosmia the price to pay in an immune-induced scorched-earth policy against COVID-19? Med Hypotheses 143:109881. https://doi.org/10.1016/j.mehy.2020.109881CrossRefPubMedPubMedCentral

56.

Borders AS, Getchell ML, Etscheidt JT, van Rooijen N, Cohen DA, Getchell TV (2007) Macrophage depletion in the murine olfactory epithelium leads to increased neuronal death and decreased neurogenesis. J Comp Neurol 501(2):206–218. https://doi.org/10.1002/cne.21252CrossRefPubMed

57.

Othman BA, Maulud SQ, Jalal PJ, Abdulkareem SM, Ahmed JQ, Dhawan M et al (2012) Olfactory dysfunction as a post-infectious symptom of SARS-CoV-2 infection. Ann Med Surg 2022(75):103352. https://doi.org/10.1016/j.amsu.2022.103352CrossRef

58.

Yamagishi M, Fujiwara M, Nakamura H (1994) Olfactory mucosal findings and clinical course in patients with olfactory disorders following upper respiratory viral infection. Rhinology 32(3):113–118PubMed

59.

Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H et al (2007) Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope 117(2):272–277. https://doi.org/10.1097/01.mlg.0000249922.37381.1eCrossRefPubMedPubMedCentral

60.

Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT et al (1992) Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 357(6377):420–422. https://doi.org/10.1038/357420a0CrossRefPubMedPubMedCentral

61.

Bertram S, Heurich A, Lavender H, Gierer S, Danisch S, Perin P et al (2012) Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts. PLoS ONE 7(4):e35876. https://doi.org/10.1371/journal.pone.0035876CrossRefPubMedPubMedCentral

62.

Sims AC, Baric RS, Yount B, Burkett SE, Collins PL, Pickles RJ (2005) Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol 79(24):15511–15524. https://doi.org/10.1128/jvi.79.24.15511-15524.2005CrossRefPubMedPubMedCentral

63.

Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203(2):631–637. https://doi.org/10.1002/path.1570CrossRefPubMedPubMedCentral

64.

Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN et al (2020) SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 181(5):1016–35.e19. https://doi.org/10.1016/j.cell.2020.04.035CrossRefPubMedPubMedCentral

65.

Solbu TT, Holen T (2012) Aquaporin pathways and mucin secretion of Bowman’s glands might protect the olfactory mucosa. Chem Senses 37(1):35–46. https://doi.org/10.1093/chemse/bjr063CrossRefPubMed

66.

Fodoulian L, Tuberosa J, Rossier D, Boillat M, Kan C, Pauli V et al (2020) SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience 23(12):101839. https://doi.org/10.1016/j.isci.2020.101839CrossRefPubMedPubMedCentral

67.

Sedaghat Z, Karimi N (2020) Guillain Barre syndrome associated with COVID-19 infection: a case report. J Clin Neurosci 76:233–235. https://doi.org/10.1016/j.jocn.2020.04.062CrossRefPubMedPubMedCentral

68.

Gane SB, Kelly C, Hopkins C (2020) Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology 58(3):299–301. https://doi.org/10.4193/Rhin20.114CrossRefPubMed

69.

Niazkar HR, Zibaee B, Nasimi A, Bahri N (2020) The neurological manifestations of COVID-19: a review article. Neurol Sci 41(7):1667–1671. https://doi.org/10.1007/s10072-020-04486-3CrossRefPubMedPubMedCentral

70.

Xydakis MS, Dehgani-Mobaraki P, Holbrook EH, Geisthoff UW, Bauer C, Hautefort C et al (2020) Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis 20(9):1015–1016. https://doi.org/10.1016/s1473-3099(20)30293-0CrossRefPubMedPubMedCentral

71.

Moein ST, Hashemian SM, Mansourafshar B, Khorram-Tousi A, Tabarsi P, Doty RL (2020) Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol 10(8):944–950. https://doi.org/10.1002/alr.22587CrossRefPubMedPubMedCentral

72.

Lorenzo Villalba N, Maouche Y, Alonso Ortiz MB, Cordoba Sosa Z, Chahbazian JB, Syrovatkova A et al (2020) Anosmia and dysgeusia in the absence of other respiratory diseases: should COVID-19 infection be considered? Eur J Case Rep Intern Med 7(4):001641. https://doi.org/10.12890/2020_001641CrossRefPubMedPubMedCentral

73.

Rashid RA, Zgair A, Al-Ani RM (2021) Effect of nasal corticosteroid in the treatment of anosmia due to COVID-19: a randomised double-blind placebo-controlled study. Am J Otolaryngol 42(5):103033. https://doi.org/10.1016/j.amjoto.2021.103033CrossRefPubMedPubMedCentral

74.

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q et al (2020) Neurologic manifestations of hospitalized patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol 77(6):683–690. https://doi.org/10.1001/jamaneurol.2020.1127CrossRefPubMed

75.

Butowt R, Bilinska K (2020) SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci 11(9):1200–1203. https://doi.org/10.1021/acschemneuro.0c00172CrossRefPubMed

76.

Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 14(2):185–192. https://doi.org/10.1007/s11684-020-0754-0CrossRefPubMedPubMedCentral

77.

Krolewski RC, Packard A, Schwob JE (2013) Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium. J Comp Neurol 521(4):833–859. https://doi.org/10.1002/cne.23204CrossRefPubMed

78.

Heydel JM, Coelho A, Thiebaud N, Legendre A, Le Bon AM, Faure P et al (2013) Odorant-binding proteins and xenobiotic metabolizing enzymes: implications in olfactory perireceptor events. Anatomical Record (Hoboken, NJ: 2007) 296(9):1333–1345. https://doi.org/10.1002/ar.22735CrossRef

79.

Mollica V, Rizzo A, Massari F (2020) The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer. Future oncology (London, England). 16(27):2029–2033. https://doi.org/10.2217/fon-2020-0571CrossRef

80.

Thunders M, Delahunt B (2020) Gene of the month: TMPRSS2 (transmembrane serine protease 2). J Clin Pathol 73(12):773–776. https://doi.org/10.1136/jclinpath-2020-206987CrossRefPubMed

81.

Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC et al (2001) Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Can Res 61(4):1686–1692

82.

Zmora P, Moldenhauer AS, Hofmann-Winkler H, Pöhlmann S (2015) TMPRSS2 isoform 1 activates respiratory viruses and is expressed in viral target cells. PLoS ONE 10(9):e0138380. https://doi.org/10.1371/journal.pone.0138380CrossRefPubMedPubMedCentral

83.

Bertram S, Dijkman R, Habjan M, Heurich A, Gierer S, Glowacka I et al (2013) TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J Virol 87(11):6150–6160. https://doi.org/10.1128/jvi.03372-12CrossRefPubMedPubMedCentral

84.

Chen YW, Lee MS, Lucht A, Chou FP, Huang W, Havighurst TC et al (2010) TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. Am J Pathol 176(6):2986–2996. https://doi.org/10.2353/ajpath.2010.090665CrossRefPubMedPubMedCentral

85.

Wettstein L, Kirchhoff F, Münch J (2022) The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment. Int J Mol Sci. https://doi.org/10.3390/ijms23031351CrossRefPubMedPubMedCentral

86.

Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z et al (2020) Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181(4):894-904.e9. https://doi.org/10.1016/j.cell.2020.03.045CrossRefPubMedPubMedCentral

87.

Lei C, Qian K, Li T, Zhang S, Fu W, Ding M et al (2020) Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat Commun 11(1):2070. https://doi.org/10.1038/s41467-020-16048-4CrossRefPubMedPubMedCentral

88.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY). 367(6483):1260–1263. https://doi.org/10.1126/science.abb2507CrossRef

89.

Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by the novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J Virol. https://doi.org/10.1128/jvi.00127-20CrossRefPubMedPubMedCentral

90.

Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (2020) The proximal origin of SARS-CoV-2. Nat Med 26(4):450–452. https://doi.org/10.1038/s41591-020-0820-9CrossRefPubMedPubMedCentral

91.

Michel CJ, Mayer C, Poch O, Thompson JD (2020) Characterization of accessory genes in coronavirus genomes. Virol J 17(1):131. https://doi.org/10.1186/s12985-020-01402-1CrossRefPubMedPubMedCentral

92.

Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I et al (2020) Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci USA 117(13):7001–7003. https://doi.org/10.1073/pnas.2002589117CrossRefPubMedPubMedCentral

93.

Hoffmann M, Kleine-Weber H, Pöhlmann S (2020) A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell 78(4):779–84.e5. https://doi.org/10.1016/j.molcel.2020.04.022CrossRefPubMedPubMedCentral

94.

Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 82(15):7264–7275. https://doi.org/10.1128/jvi.00737-08CrossRefPubMedPubMedCentral

95.

Strotmann J, Breer H (2011) Internalization of odorant-binding proteins into the mouse olfactory epithelium. Histochem Cell Biol 136(3):357–369. https://doi.org/10.1007/s00418-011-0850-yCrossRefPubMed

96.

Abbasi AZ, Kiyani DA, Hamid SM, Saalim M, Fahim A, Jalal N (2021) Spiking dependence of SARS-CoV-2 pathogenicity on TMPRSS2. J Med Virol 93(7):4205–4218. https://doi.org/10.1002/jmv.26911CrossRefPubMedPubMedCentral

97.

Zhao H, Lu L, Peng Z, Chen LL, Meng X, Zhang C et al (2022) SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells. Emerg microb Infect 11(1):277–283. https://doi.org/10.1080/22221751.2021.2023329CrossRef

98.

Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23(1):3–20. https://doi.org/10.1038/s41580-021-00418-xCrossRefPubMed

99.

Saito A, Irie T, Suzuki R, Maemura T, Nasser H, Uriu K et al (2022) Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature 602(7896):300–306. https://doi.org/10.1038/s41586-021-04266-9CrossRefPubMed

100.

Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R, Swann OC et al (2021) The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol 6(7):899–909. https://doi.org/10.1038/s41564-021-00908-wCrossRefPubMed

101.

Arora P, Sidarovich A, Krüger N, Kempf A, Nehlmeier I, Graichen L et al (2021) B.1.617.2 enters and fuses lung cells with increased efficiency and evades antibodies induced by infection and vaccination. Cell Rep 37(2):109825. https://doi.org/10.1016/j.celrep.2021.109825CrossRefPubMedPubMedCentral

102.

Zhang J, Xiao T, Cai Y, Lavine CL, Peng H, Zhu H et al (2021) Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science (New York, NY). 374(6573):1353–1360. https://doi.org/10.1126/science.abl9463CrossRef

103.

Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D et al (2021) Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia. Nature 594(7861):88–93. https://doi.org/10.1038/s41586-021-03491-6CrossRefPubMedPubMedCentral

104.

Khan H, Winstone H, Jimenez-Guardeño JM, Graham C, Doores KJ, Goujon C et al (2021) TMPRSS2 promotes SARS-CoV-2 evasion from NCOA7-mediated restriction. PLoS Pathog 17(11):e1009820. https://doi.org/10.1371/journal.ppat.1009820CrossRefPubMedPubMedCentral

105.

Hoffmann M, Mösbauer K, Hofmann-Winkler H, Kaul A, Kleine-Weber H, Krüger N et al (2020) Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature 585(7826):588–590. https://doi.org/10.1038/s41586-020-2575-3CrossRefPubMed

106.

SeyedAlinaghi S, Mehrtak M, MohsseniPour M, Mirzapour P, Barzegary A, Habibi P et al (2021) Genetic susceptibility of COVID-19: a systematic review of current evidence. Eur J Med Res 26(1):46. https://doi.org/10.1186/s40001-021-00516-8CrossRefPubMedPubMedCentral

107.

Ejaz H, Alsrhani A, Zafar A, Javed H, Junaid K, Abdalla AE et al (2020) COVID-19 and comorbidities: deleterious impact on infected patients. J Infect Public Health 13(12):1833–1839. https://doi.org/10.1016/j.jiph.2020.07.014CrossRefPubMedPubMedCentral

108.

Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P et al (2020) Comorbidity and its Impact on Patients with COVID-19. SN Comp Clin Med 2(8):1069–1076. https://doi.org/10.1007/s42399-020-00363-4CrossRef

109.

Muschitz C, Trummert A, Berent T, Laimer N, Knoblich L, Bodlaj G et al (2021) Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms. Wien Klin Wochenschr 133(17–18):973–978. https://doi.org/10.1007/s00508-021-01867-2CrossRefPubMedPubMedCentral

110.

Saengsiwaritt W, Jittikoon J, Chaikledkaew U, Udomsinprasert W (2022) Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID-19 severity: a systematic review with meta-analysis. Rev Med Virol. https://doi.org/10.1002/rmv.2323CrossRefPubMed

111.

Pandey RK, Srivastava A, Singh PP, Chaubey G (2022) Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations. Infect Genet Evol 98:105206. https://doi.org/10.1016/j.meegid.2022.105206CrossRefPubMedPubMedCentral

112.

Paniri A, Hosseini MM, Akhavan-Niaki H (2021) First comprehensive computational analysis of functional consequences of TMPRSS2 SNPs in susceptibility to SARS-CoV-2 among different populations. J Biomol Struct Dyn 39(10):3576–3593. https://doi.org/10.1080/07391102.2020.1767690CrossRefPubMed

113.

Bhanushali A, Rao P, Raman V, Kokate P, Ambekar A, Mandva S et al (2018) Status of TMPRSS2-ERG fusion in prostate cancer patients from India: correlation with clinico-pathological details and TMPRSS2 Met160Val polymorphism. Prostate Int 6(4):145–150. https://doi.org/10.1016/j.prnil.2018.03.004CrossRefPubMedPubMedCentral

114.

Maekawa S, Suzuki M, Arai T, Suzuki M, Kato M, Morikawa T et al (2014) TMPRSS2 Met160Val polymorphism: significant association with sporadic prostate cancer, but not with latent prostate cancer in Japanese men. Int J Urol 21(12):1234–1238. https://doi.org/10.1111/iju.12578CrossRefPubMed

115.

Giri VN, Ruth K, Hughes L, Uzzo RG, Chen DY, Boorjian SA et al (2011) Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high-risk men: effect of TMPRSS2 Met160Val. BJU Int 107(3):466–470. https://doi.org/10.1111/j.1464-410X.2010.09522.xCrossRefPubMed

116.

Lubieniecka JM, Cheteri MK, Stanford JL, Ostrander EA (2004) Met160Val polymorphism in the TRMPSS2 gene and risk of prostate cancer in a population-based case-control study. Prostate 59(4):357–359. https://doi.org/10.1002/pros.20005CrossRefPubMed

117.

Wulandari L, Hamidah B, Pakpahan C, Damayanti NS, Kurniati ND, Adiatmaja CO et al (2021) Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients. Human Genom 15(1):29. https://doi.org/10.1186/s40246-021-00330-7CrossRef

118.

Karimian M, Aftabi Y, Mazoochi T, Babaei F, Khamechian T, Boojari H et al (2018) Survivin polymorphisms and susceptibility to prostate cancer: a genetic association study and an in silico analysis. EXCLI J 17:479–491PubMedPubMedCentral

119.

Mobasseri N, Babaei F, Karimian M, Nikzad H (2018) Androgen receptor (AR)-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis. EXCLI J 17:1167–1179PubMedPubMedCentral

120.

Bafrani HH, Ahmadi M, Jahantigh D, Karimian M (2019) Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis. J Cell Biochem 120(10):18020–18030CrossRef

121.

Mobasseri N, Nikzad H, Karimian M (2019) Protective effect of oestrogen receptor α-PvuII transition against idiopathic male infertility: a case-control study and meta-analysis. Reprod Biomed Online 38(4):588–598CrossRef

122.

Karimian M, Momeni A, Farmohammadi A, Behjati M, Jafari M, Raygan F (2020) Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: a genetic association study and a structural analysis. J Cell Biochem 121(5–6):3345–3357CrossRef

123.

Karimian M, Behjati M, Barati E, Ehteram T, Karimian A (2020) CYP1A1 and GSTs common gene variations and presbycusis risk: a genetic association analysis and a bioinformatics approach. Environ Sci Pollut Res 27(34):42600–42610CrossRef

124.

Karimian M, Ghazaey Zidanloo S, Jahantigh D (2022) Influence of FOXP3 gene polymorphisms on the risk of preeclampsia: a meta-analysis and a bioinformatic approach. Clin Exp Hypertens 44(3):280–290CrossRef

125.

Zamani-Badi T, Karimian M, Azami-Tameh A, Nikzad H (2019) Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population. Hum Fertil 22:111–117CrossRef

126.

Karimian M, Hosseinzadeh CA (2018) Human MTHFR-G1793A transition may be a protective mutation against male infertility: a genetic association study and in silico analysis. Hum Fertil 21(2):128–136CrossRef

127.

Torre-Fuentes L, Matías-Guiu J, Hernández-Lorenzo L, Montero-Escribano P, Pytel V, Porta-Etessam J et al (2021) ACE2, TMPRSS2, and Furin variants and SARS-CoV-2 infection in Madrid, Spain. J Med Virol 93(2):863–869. https://doi.org/10.1002/jmv.26319CrossRefPubMed

128.

Monticelli M, Hay Mele B, Benetti E, Fallerini C, Baldassarri M, Furini S et al (2021) Protective role of a TMPRSS2 variant on severe COVID-19 outcome in young males and elderly women. Genes. https://doi.org/10.3390/genes12040596CrossRefPubMedPubMedCentral

129.

Curtis D (2020) Variants in ACE2 and TMPRSS2 genes are not major determinants of COVID-19 severity in UK Biobank Subjects. Hum Hered 85(2):66–68. https://doi.org/10.1159/000515200CrossRefPubMed

130.

Schönfelder K, Breuckmann K, Elsner C, Dittmer U, Fistera D, Herbstreit F et al (2021) Transmembrane serine protease 2 polymorphisms and susceptibility to severe acute respiratory syndrome Coronavirus Type 2 Infection: a German case-control study. Front Genet 12:667231. https://doi.org/10.3389/fgene.2021.667231CrossRefPubMedPubMedCentral

131.

Ravikanth V, Sasikala M, Naveen V, Latha SS, Parsa KVL, Vijayasarathy K et al (2021) A variant in TMPRSS2 is associated with decreased disease severity in COVID-19. Meta Gene 29:100930. https://doi.org/10.1016/j.mgene.2021.100930CrossRefPubMed

132.

Akin S, Schriek P, van Nieuwkoop C, Neuman RI, Meynaar I, van Helden EJ et al (2022) A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity. J Hypertens 40(3):606–614. https://doi.org/10.1097/hjh.0000000000003054CrossRefPubMed

133.

Báez-Santos YM, St John SE, Mesecar AD (2015) The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res 115:21–38. https://doi.org/10.1016/j.antiviral.2014.12.015CrossRefPubMed

134.

Shen LW, Qian MQ, Yu K, Narva S, Yu F, Wu YL et al (2020) Inhibition of Influenza A virus propagation by benzoselenoxanthenes stabilizing TMPRSS2 Gene G-quadruplex and hence down-regulating TMPRSS2 expression. Sci Rep 10(1):7635. https://doi.org/10.1038/s41598-020-64368-8CrossRefPubMedPubMedCentral

135.

Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW et al (2015) Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 116:76–84. https://doi.org/10.1016/j.antiviral.2015.01.011CrossRefPubMedPubMedCentral

136.

Yamaya M, Shimotai Y, Hatachi Y, Lusamba Kalonji N, Tando Y, Kitajima Y et al (2015) The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther 33:66–74. https://doi.org/10.1016/j.pupt.2015.07.001CrossRefPubMedPubMedCentral

137.

Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F (2010) Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol 84(24):12658–12664. https://doi.org/10.1128/jvi.01542-10CrossRefPubMedPubMedCentral

138.

Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S et al (2011) 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 85(9):4122–4134. https://doi.org/10.1128/jvi.02232-10CrossRefPubMedPubMedCentral

139.

Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S (2012) Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol 86(12):6537–6545. https://doi.org/10.1128/jvi.00094-12CrossRefPubMedPubMedCentral

140.

Ikeda S, Manabe M, Muramatsu T, Takamori K, Ogawa H (1988) Protease inhibitor therapy for recessive dystrophic epidermolysis bullosa. In vitro effect and clinical trial with camostat mesylate. J Am Acad Dermatol 18(6):1246–1252. https://doi.org/10.1016/s0190-9622(88)70130-9CrossRefPubMed

141.

Ohkoshi M, Fujii S (1983) Effect of the synthetic protease inhibitor [N, N-dimethylcarbamoyl-methyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate on carcinogenesis by 3-methylcholanthrene in mouse skin. J Natl Cancer Inst 71(5):1053–1057PubMed

142.

Ohkoshi M, Oka T (1984) Clinical experience with a protease inhibitor [N, N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate for prevention of recurrence of carcinoma of the mouth and in treatment of terminal carcinoma. J Maxillofac Surg 12(4):148–152. https://doi.org/10.1016/s0301-0503(84)80235-0CrossRefPubMed

143.

Sai JK, Suyama M, Kubokawa Y, Matsumura Y, Inami K, Watanabe S (2010) Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease. J Gastroenterol 45(3):335–341. https://doi.org/10.1007/s00535-009-0148-1CrossRefPubMed

144.

Yamawaki H, Futagami S, Kaneko K, Agawa S, Higuchi K, Murakami M et al (2019) Camostat mesilate, pancrelipase, and rabeprazole combination therapy improves epigastric pain in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme abnormalities. Digestion 99(4):283–292. https://doi.org/10.1159/000492813CrossRefPubMed

145.

Ramsey ML, Nuttall J, Hart PA (2019) A phase 1/2 trial to evaluate the pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC). Trials 20(1):501. https://doi.org/10.1186/s13063-019-3606-yCrossRefPubMedPubMedCentral

146.

Göke B, Stöckmann F, Müller R, Lankisch PG, Creutzfeldt W (1984) Effect of a specific serine protease inhibitor on the rat pancreas: systemic administration of camostate and exocrine pancreatic secretion. Digestion 30(3):171–178. https://doi.org/10.1159/000199102CrossRefPubMed

147.

Adler G, Müllenhoff A, Koop I, Bozkurt T, Göke B, Beglinger C et al (1988) Stimulation of pancreatic secretion in man by a protease inhibitor (camostate). Eur J Clin Invest 18(1):98–104. https://doi.org/10.1111/j.1365-2362.1988.tb01173.xCrossRefPubMed

148.

Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M et al (1986) Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol 41(2):155–162. https://doi.org/10.1254/jjp.41.155CrossRefPubMed

149.

Hiraishi M, Yamazaki Z, Ichikawa K, Kanai F, Idezuki Y, Onishi K et al (1988) Plasma collection using nafamostat mesilate and dipyridamole as an anticoagulant. Int J Artif Organs 11(3):212–216CrossRef

150.

Hirota M, Shimosegawa T, Kitamura K, Takeda K, Takeyama Y, Mayumi T et al (2020) Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial. J Gastroenterol 55(3):342–352. https://doi.org/10.1007/s00535-019-01644-zCrossRefPubMed

151.

Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue JI et al (2016) Identification of nafamostat as a potent inhibitor of middle east respiratory syndrome Coronavirus S protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob Agents Chemother 60(11):6532–6539. https://doi.org/10.1128/aac.01043-16CrossRefPubMedPubMedCentral

152.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England) 395(10224):565–574. https://doi.org/10.1016/s0140-6736(20)30251-8CrossRef

153.

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181(2):281–92.e6. https://doi.org/10.1016/j.cell.2020.02.058CrossRefPubMedPubMedCentral

154.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M et al (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3):269–271. https://doi.org/10.1038/s41422-020-0282-0CrossRefPubMedPubMedCentral

Title: Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2
Authors: Ali Karimian
Mohaddeseh Behjati
Mohammad Karimian
Publication date: 08-08-2022
Publisher: Springer Vienna
Keywords: Smelling Disorder
SARS-CoV-2
Smelling Disorder
COVID-19
Anosmia
Published in: Archives of Virology / Issue 10/2022
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-022-05545-0

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Molecular mechanisms involved in anosmia induced by SARS-CoV-2, with a focus on the transmembrane serine protease TMPRSS2

Abstract

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Abstract

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