Smoke, nicotine, opioids, and cannabinoids effects on the ACE2 protein level and possibility of COVID-19 infection: Suggesting potential preventives and therapeutics
Introduction. The coronavirus caused the pandemic COVID-19 that has an extensive influence in the world. The virus enters and infects body cells through superficial protein ACE2. Each cell possessing ACE2 is potentially vulnerable to this virus. Since the respiratory system is exposed to the environment and has ACE2, it is one of the first candidates infected by the virus. One of the considerable complications in the severe stage of COVID-19 is an intense adaptive immunological response that is detrimental to body organs. Methods. This is a review article. All relevant articles which were accessible were reviewed. Results. Some drugs of abuse may have an adverse or beneficial influence on the disease, and their simultaneity with COVID-19 is remarkable. Nicotine and cholinergic nicotinic receptor agonists seem to decrease the cell's membrane superficial ACE2 protein number; thus, they would be appropriate candidates for COVID-19 prevention and expansion. Both opioids and cannabinoids attenuate the immune system and seem to be adverse for disease incidence but can be beneficial for the severe stage of COVID19. The antitussive effect of some opioids would be advantageous. Furthermore, some opioids are substrates for ACE2 and they bind it. Therefore, they would be an appropriate candidate to design a drug covering ACE2 with a high affinity to prevent coronavirus infection. Conclusion. Some drugs, such as nicotine and opioids, may have beneficial effects on preventing or reducing COVID-19 complications.
References
1.
Karlsson J, Lanner A, Persson C. Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs. J Pharmacol Exp Ther. 1990;252(2):863–8.
2.
Chappel MC, Ferrario CM. ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1–7). Kidney International. 2006;70(1):8–10.
3.
Cabral GA. Drugs of Abuse, Immune Modulation, and AIDS. Journal of Neuroimmune Pharmacology. 2006;1(3):280–95.
4.
Steptoe A, Ussher M. Smoking, cortisol and nicotine. International Journal of Psychophysiology. 2006;59(3):228–35.
5.
Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME. Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Psychopharmacology. 1982;78(4):305–8.
6.
McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response. Drug and Alcohol Dependence. 2001;62(2):111–23.
7.
Bayer BM, Daussin S, Hernandez M, Irvin L. Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism. Neuropharmacology. 1990;29(4):369–74.
8.
Peterson PK, Sharp B, Gekker G, Brummitt C, Keane WF. Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. Journal of Clinical Investigation. 1987;80(3):824–31.
9.
Roy S, Ramakrishnan S, Loh HH, Lee NM. Chronic morphine treatment selectively suppresses macrophage colony formation in bone marrow. European Journal of Pharmacology. 1991;195(3):359–63.
10.
Mahajan SD, Schwartz SA, Shanahan TC, Chawda RP, Nair MPN. Morphine Regulates Gene Expression of α- and β-Chemokines and Their Receptors on Astroglial Cells Via the Opioid μ Receptor. The Journal of Immunology. 2002;169(7):3589–99.
11.
Carr D, France C. Immune alterations in morphine-treated rhesus monkeys. J Pharmacol Exp Ther. 1993;267(1):9–15.
12.
Beagles K, Wellstein A, Bayer B. Systemic Morphine Administration Suppresses Genes Involved in Antigen Presentation. Molecular Pharmacology. 2004;65(2):437–42.
13.
Carpenter GW, Garza HH, Gebhardt BM, Carr DJJ. Chronic Morphine Treatment Suppresses CTL-Mediated Cytolysis, Granulation, and cAMP Responses to Alloantigen. Brain, Behavior, and Immunity. 1994;8(3):185–203.
14.
Miyagi T, Chuang LF, Lam KM, Kung H fu, Wang JM, Osburn BI, et al. Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes — an instant response. Immunopharmacology. 2000;47(1):53–62.
15.
Grimm MC, Ben-Baruch A, Taub DD, Howard OMZ, Resau JH, Wang JM, et al. Opiates Transdeactivate Chemokine Receptors: δ and μ Opiate Receptor–mediated Heterologous Desensitization. The Journal of Experimental Medicine. 1998;188(2):317–25.
16.
Chao CC, Hu S, Shark KB, Sheng WS, Gekker G, Peterson PK. Activation of mu opioid receptors inhibits microglial cell chemotaxis. J Pharmacol Exp Ther. 1997;281(2):998–1004.
17.
Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin–angiotensin system. Trends in Endocrinology & Metabolism. 2004;15(4):166–9.
18.
Adcock JJ. Peripheral opioid receptors and the cough reflex. Respiratory Medicine. 1991;85:43–6.
19.
Yan YM, Shen X, Cao YK, Zhang JJ, Wang Y, Cheng YX. Discovery of Anti-2019-nCoV Agents from 38 Chinese Patent Drugs toward Respiratory Diseases via Docking Screening <strong> </strong>
20.
Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, et al. Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase. Journal of Biological Chemistry. 2002;277(17):14838–43.
21.
Pasero C. Assessment of Sedation During Opioid Administration for Pain Management. Journal of PeriAnesthesia Nursing. 2009;24(3):186–90.
22.
Pattinson KTS. Opioids and the control of respiration. British Journal of Anaesthesia. 2008;100(6):747–58.
23.
Khaleghzadeh-Ahangar H, Haghparast A. Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine. Physiology & Behavior. 2015;149:212–9.
24.
Khaleghzadeh-Ahangar H, Haghparast A. Intra-accumbal Cannabinoid Agonist Attenuated Reinstatement but not Extinction Period of Morphine-Induced Conditioned Place Preference; Evidence for Different Characteristics of Extinction Period and Reinstatement. Neurochemical Research. 2017;42(11):3321–30.
25.
Khaleghzadeh-Ahangar H, Khodagholi F, Shaerzadeh F, Haghparast A. Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats. Brain Research Bulletin. 2018;142:320–7.
26.
Khaleghzadeh‐Ahangar H, Haghparast A. Cannabinoid receptor modulation changes the accumbal neuronal responses to morphine in the reinstatement of morphine‐induced conditioned place preference. Addiction Biology. 2020;25(6).
27.
Newton CA, Chou PJ, Perkins I, Klein TW. CB1 and CB2 Cannabinoid Receptors Mediate Different Aspects of Delta-9-Tetrahydrocannabinol (THC)-Induced T Helper Cell Shift Following Immune Activation by Legionella Pneumophila Infection. Journal of Neuroimmune Pharmacology. 2009;4(1):92–102.
28.
Hojo M, Sudo Y, Ando Y, Minami K, Takada M, Matsubara T, et al. μ-Opioid Receptor Forms a Functional Heterodimer With Cannabinoid CB1 Receptor: Electrophysiological and FRET Assay Analysis. Journal of Pharmacological Sciences. 2008;108(3):308–19.
29.
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, et al. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology. 2009;203(4):737–44.
30.
Cabral GA, Staab A. Effects on the Immune System. Handbook of Experimental Pharmacology. 2005. p. 385–423.
31.
Roth MD, Tashkin DP, Whittaker KM, Choi R, Baldwin GC. Tetrahydrocannabinol suppresses immune function and enhances HIV replication in the huPBL-SCID mouse. Life Sciences. 2005;77(14):1711–22.
32.
Klein TW, Newton CA, Nakachi N, Friedman H. Δ9-Tetrahydrocannabinol Treatment Suppresses Immunity and Early IFN-γ, IL-12, and IL-12 Receptor β2 Responses toLegionella pneumophilaInfection. The Journal of Immunology. 2000;164(12):6461–6.
33.
Cai H. Sex difference and smoking predisposition in patients with COVID-19. The Lancet Respiratory Medicine. 2020;8(4):e20.
34.
Chan KK, Dorosky D, Sharma P, Abbasi SA, Dye JM, Kranz DM, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science. 2020;369(6508):1261–5.
35.
Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, et al. COVID-19 infection: the perspectives on immune responses. Cell Death & Differentiation. 2020;27(5):1451–4.
36.
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349(jan02 1):g7647–g7647.
37.
Hecht SS. Lung carcinogenesis by tobacco smoke. International Journal of Cancer. 2012;131(12):2724–32.
38.
Demling RH. Smoke inhalation lung injury: an update. Eplasty. 2008;8.
39.
Churg A, Cosio M, Wright JL. Mechanisms of cigarette smoke-induced COPD: insights from animal models. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2008;294(4):L612–31.
40.
Berlin I, Thomas D, Le Faou AL, Cornuz J. COVID-19 and Smoking. Nicotine & Tobacco Research. 2020;22(9):1650–2.
41.
Vardavas C, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tobacco Induced Diseases. 18(March).
42.
Olds JL, Kabbani N. Is nicotine exposure linked to cardiopulmonary vulnerability to COVID‐19 in the general population? The FEBS Journal. 2020;287(17):3651–5.
43.
Fu L, Wang B, Yuan T, Chen X, Ao Y, Fitzpatrick T, et al. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. Journal of Infection. 2020;80(6):656–65.
44.
Parascandola M, Xiao L. Tobacco and the lung cancer epidemic in China. Translational Lung Cancer Research. 2019;8(S1):S21–30.
45.
Hu Z, Song C, Xu C, Jin G, Chen Y, Xu X, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Science China Life Sciences. 2020;63(5):706–11.
46.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054–62.
47.
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. The Lancet. 2020;395(10223):497–506.
48.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020;8(5):475–81.
49.
Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. The Lancet. 2020;395(10225):689–97.
50.
Liu W, Tao ZW, Wang L, Yuan ML, Liu K, Zhou L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese Medical Journal. 133(9):1032–8.
51.
Moosazadeh M, Ziaaddini H, Mirzazadeh A, Ashrafi-Asgarabad A, Haghdoost AA. Metaanalysis of smoking prevalence in Iran. AHJ. 2013;5(3–4).
52.
Mohammadian M, Sarrafzadegan N, Roohafza HR, Sadeghi M, Hasanzadeh A, Rejali M. A Comparative Study On The Prevalence And Related Factors Of Cigarette Smoking In Iran And Other Asian Countries: Results Of Isfahan Cohort Study (ICS. WCRJ. 2018;5(4).
53.
Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, et al. Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respiratory Research. 2007;8(1).
54.
Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia. Journal of Virology. 2005;79(23):14614–21.
55.
Cai G. Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung Gene Expression of ACE2, the Receptor of 2019-nCov.
56.
Smith JC, Sausville EL, Girish V, Yuan ML, John KM, Sheltzer JM. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract.
57.
Brake SJ, Barnsley K, Lu W, McAlinden KD, Eapen MS, Sohal SS. Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19). Journal of Clinical Medicine. 9(3):841.
58.
Hikmet F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C. The protein expression profile of ACE2 in human tissues. Molecular Systems Biology. 2020;16(7).
59.
Conti-Fine BM, Navaneetham D, Lei S, Maus ADJ. Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity? European Journal of Pharmacology. 2000;393(1–3):279–94.
60.
Kitamura S. Effects of cigarette smoking on metabolic events in the lung. Environmental Health Perspectives. 1987;72:283–96.
61.
Sugiyama Y, Yotsumoto H, Takaku F. Increase of Serum Angiotensin-Converting Enzyme Level after Exposure to Cigarette Smoke and Nicotine Infusion in Dogs. Respiration. 1986;49(4):292–5.
62.
Koka V, Huang XR, Chung ACK, Wang W, Truong LD, Lan HY. Angiotensin II Up-Regulates Angiotensin I-Converting Enzyme (ACE), but Down-Regulates ACE2 via the AT1-ERK/p38 MAP Kinase Pathway. The American Journal of Pathology. 2008;172(5):1174–83.
63.
Ferrari MFR, Raizada MK, Fior-Chadi DR. Nicotine Modulates the Renin–Angiotensin System of Cultured Neurons and Glial Cells from Cardiovascular Brain Areas of Wistar Kyoto and Spontaneously Hypertensive Rats. Journal of Molecular Neuroscience. 2007;33(3):284–93.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
