Targeting COVID-19 in Parkinson’s Patients: Drugs Repurposed

Firoz       Anwar; Salma       Naqvi; Fahad    A.    Al-Abbasi; Nauroz       Neelofar; Vikas       Kumar; Ankit       Sahoo; Mohammad    Amjad    Kamal
doi:10.2174/0929867327666200903115138
Abstract

The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken the globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson's disease (PD).
Alteration in dopaminergic neurons and deficiency of dopamine in PD patients are the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common drugs under trial for COVID-19 are remdesivir, favipiravir, chloroquine and hydroxychloroquine, azithromycin along with adjunct drugs like amantadine with some monoclonal antibodies.
Presently, clinically US FDA approved drugs in PD include Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), amantadine and antimuscarinic drugs. The drugs have established mechanisms of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects.
Conclusion and relevance of this review focus on the drugs that can be tried on PD patients with SAR CoV-2 infection, in particular, amantadine that has been approved by all the developed countries as a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and anti- Parkinson properties. To deal with the significant prognostic adverse effect of SARS-CoV-2 on PD, the present-day treatment options, clinical presentation and various mechanisms are the need of the hour.
Keywords: COVID-19, Parkinson disease, amantadine, SARS-CoV-2, treatment, pH disturbance.
« Previous Next »
[1] 
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in china, 2019. N. Engl. J. Med.,  2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID:  31978945] 
[2] 
Tanne, J.H.; Hayasaki, E.; Zastrow, M.; Pulla, P.; Smith, P.; Rada, A.G. Covid-19: how doctors and healthcare systems are tackling coronavirus worldwide. BMJ,  2020, 368, m1090.
[http://dx.doi.org/10.1136/bmj.m1090] [PMID:  32188598] 
[3] 
Ye, Z-W.; Yuan, S.; Yuen, K-S.; Fung, S-Y.; Chan, C-P.; Jin, D-Y. Zoonotic origins of human coronaviruses. Int. J. Biol. Sci.,  2020, 16(10), 1686-1697.
[http://dx.doi.org/10.7150/ijbs.45472] [PMID:  32226286] 
[4] 
Ashour, H.M.; Elkhatib, W.F.; Rahman, M.M.; Elshabrawy, H.A. Insights into the recent 2019 novel Coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathogens,  2020, 9(3), 186.
[http://dx.doi.org/10.3390/pathogens9030186] [PMID:  32143502] 
[5] 
Li, X.; Zai, J.; Zhao, Q.; Nie, Q.; Li, Y.; Foley, B.T.; Chaillon, A. Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2. J. Med. Virol.,  2020, 92(6), 602-611.
[http://dx.doi.org/10.1002/jmv.25731] [PMID:  32104911] 
[6] 
Lai, C-C.; Shih, T-P.; Ko, W-C.; Tang, H-J.; Hsueh, P-R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int. J. Antimicrob. Agents,  2020, 55(3), 105924.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID:  32081636] 
[7] 
Lauer, S.A.; Grantz, K.H.; Bi, Q.; Jones, F.K.; Zheng, Q.; Meredith, H.R.; Azman, A.S.; Reich, N.G.; Lessler, J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann. Intern. Med.,  2020, 172(9), 577-582.
[http://dx.doi.org/10.7326/M20-0504] [PMID:  32150748] 
[8] 
Wu, Z.; McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA,  2020, 323(13), 1239-1242.
[http://dx.doi.org/10.1001/jama.2020.2648] [PMID:  32091533] 
[9] 
Wehbe, Z.; Hammoud, S.; Soudani, N.; Zaraket, H.; El-Yazbi, A.; Eid, A.H. Molecular insights into SARS COV-2 interaction with cardiovascular disease: role of RAAS and MAPK signaling. Front. Pharmacol.,  2020, 11, 836.
[http://dx.doi.org/10.3389/fphar.2020.00836] [PMID:  32581799] 
[10] 
Li, J-Y.; You, Z.; Wang, Q.; Zhou, Z-J.; Qiu, Y.; Luo, R.; Ge, X-Y. The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. Microbes Infect.,  2020, 22(2), 80-85.
[http://dx.doi.org/10.1016/j.micinf.2020.02.002] [PMID:  32087334] 
[11] 
Balestrino, R.; Schapira, A.H.V. Parkinson disease. Eur. J. Neurol.,  2020, 27(1), 27-42.
[http://dx.doi.org/10.1111/ene.14108] [PMID:  31631455] 
[12] 
Jia, L.; Quan, M.; Fu, Y.; Zhao, T.; Li, Y.; Wei, C.; Tang, Y.; Qin, Q.; Wang, F.; Qiao, Y.; Shi, S.; Wang, Y.J.; Du, Y.; Zhang, J.; Zhang, J.; Luo, B.; Qu, Q.; Zhou, C.; Gauthier, S.; Jia, J. Group for the Project of Dementia Situation in China. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol.,  2020, 19(1), 81-92.
[http://dx.doi.org/10.1016/S1474-4422(19)30290-X] [PMID:  31494009] 
[13] 
Reeve, A.; Simcox, E.; Turnbull, D. Ageing and parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res. Rev.,  2014, 14(100), 19-30.
[http://dx.doi.org/10.1016/j.arr.2014.01.004] [PMID:  24503004] 
[14] 
Dorsey, E.R.; Constantinescu, R.; Thompson, J.P.; Biglan, K.M.; Holloway, R.G.; Kieburtz, K.; Marshall, F.J.; Ravina, B.M.; Schifitto, G.; Siderowf, A.; Tanner, C.M. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology,  2007, 68(5), 384-386.
[http://dx.doi.org/10.1212/01.wnl.0000247740.47667.03] [PMID:  17082464] 
[15] 
Liu, K.; Chen, Y.; Lin, R.; Han, K. Clinical features of COVID-19 in elderly patients: a comparison with young and middle-aged patients. J. Infect.,  2020, 80(6), e14-e18.
[http://dx.doi.org/10.1016/j.jinf.2020.03.005] [PMID:  32171866] 
[16] 
Liu, Y.; Gayle, A.A.; Wilder-Smith, A.; Rocklöv, J. The
reproductive number of COVID-19 is higher compared to
SARS coronavirus. J. Travel Med.,  2020, 27(2) taaa021.
[http://dx.doi.org/10.1093/jtm/taaa021] [PMID: 32052846] 
[17] 
Handa, K.; Kiyohara, S.; Yamakawa, T.; Ishikawa, K.; Hosonuma, M.; Sakai, N.; Karakawa, A.; Chatani, M.; Tsuji, M.; Inagaki, K.; Kiuchi, Y.; Takami, M.; Negishi-Koga, T. Bone loss caused by dopaminergic degeneration and levodopa treatment in Parkinson’s disease model mice. Sci. Rep.,  2019, 9(1), 13768.
[http://dx.doi.org/10.1038/s41598-019-50336-4] [PMID:  31551490] 
[18] 
Chaudhuri, K.R.; Fung, V.S.C. Fast Facts: Parkinson’s Disease, 4th ed; Health Press Limited: London, 2016. 
[19] 
Dafsari, H.S.; Petry-Schmelzer, J.N.; Ray-Chaudhuri, K.; Ashkan, K.; Weis, L.; Dembek, T.A.; Samuel, M.; Rizos, A.; Silverdale, M.; Barbe, M.T.; Fink, G.R.; Evans, J.; Martinez-Martin, P.; Antonini, A.; Visser-Vandewalle, V.; Timmermann, L. EUROPAR; IPMDS Non Motor PD Study Group. Non-motor outcomes of subthalamic stimulation in parkinson’s disease depend on location of active contacts. Brain Stimul.,  2018, 11(4), 904-912.
[http://dx.doi.org/10.1016/j.brs.2018.03.009] [PMID:  29655586] 
[20] 
Inzelberg, R.; Flash, S.; Friedman, E.; Azizi, E. Cutaneous malignant melanoma and parkinson disease: common pathways? Ann. Neurol.,  2016, 80(6), 811-820.
[http://dx.doi.org/10.1002/ana.24802] [PMID:  27761938] 
[21] 
Trenkwalder, C.; Kuoppamäki, M.; Vahteristo, M.; Müller, T.; Ellmén, J. Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial. Neurology,  2019, 92(13), e1487-e1496.
[http://dx.doi.org/10.1212/WNL.0000000000007173] [PMID:  30824559] 
[22] 
Daidone, F.; Montioli, R.; Paiardini, A.; Cellini, B.; Macchiarulo, A.; Giardina, G.; Bossa, F.; Borri Voltattorni, C. Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors. PLoS One,  2012, 7(2), e31610.
[http://dx.doi.org/10.1371/journal.pone.0031610] [PMID:  22384042] 
[23] 
Uddin, M.S.; Rashid, M. Advances in Neuropharmacology: Drugs and Therapeutics, 1st ed; Apple Academic Press: Boca Raton, 2020. 
[http://dx.doi.org/10.1201/9780429242717] 
[24] 
Jost, W.H.; Altmann, C.; Fiesel, T.; Becht, B.; Ringwald, S.; Hoppe, T. Influence of levodopa on orthostatic hypotension in parkinson’s disease. Neurol. Neurochir. Pol.,  2020, 54(2), 200-203.
[http://dx.doi.org/10.5603/PJNNS.a2020.0019] [PMID:  32219811] 
[25] 
Nakaki, T. Chapter 11- Drugs that affect autonomic functions or the extrapyramidal system. In:Side Effects of Drugs Annual; Ray, S.D., Ed.; Elsevier: Amsterdam, 2017, Vol. 39, pp. 133-144.
[http://dx.doi.org/10.1016/bs.seda.2017.06.024] 
[26] 
van der Velden, R.M.J.; Broen, M.P.G.; Kuijf, M.L.; Leentjens, A.F.G. Frequency of mood and anxiety fluctuations in Parkinson’s disease patients with motor fluctuations: A systematic review. Mov. Disord.,  2018, 33(10), 1521-1527.
[http://dx.doi.org/10.1002/mds.27465] [PMID:  30225905] 
[27] 
Ha, S.K.; Lee, J.A.; Cho, E.J.; Choi, I. Effects of catechol o-methyl transferase inhibition on anti-inflammatory activity of luteolin metabolites. J. Food Sci.,  2017, 82(2), 545-552.
[http://dx.doi.org/10.1111/1750-3841.13620] [PMID:  28071803] 
[28] 
Finberg, J.P.M. Inhibitors of MAO-B and COMT: their effects on brain dopamine levels and uses in parkinson’s disease. J. Neural Transm. (Vienna),  2019, 126(4), 433-448.
[http://dx.doi.org/10.1007/s00702-018-1952-7] [PMID:  30386930] 
[29] 
Lv, X.; Wang, X-X.; Hou, J.; Fang, Z-Z.; Wu, J-J.; Cao, Y-F.; Liu, S-W.; Ge, G-B.; Yang, L. Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases. Toxicol. Appl. Pharmacol.,  2016, 301, 42-49.
[http://dx.doi.org/10.1016/j.taap.2016.04.009] [PMID:  27089846] 
[30] 
Katsaiti, I.; Nixon, J. Are There benefits in adding catechol-o methyltransferase inhibitors in the pharmacotherapy of parkinson’s disease patients? A systematic review. J. Parkinsons Dis.,  2018, 8(2), 217-231.
[http://dx.doi.org/10.3233/JPD-171225] [PMID:  29614697] 
[31] 
Castro Caldas, A.; Teodoro, T.; Ferreira, J.J. The launch of opicapone for Parkinson’s disease: negatives versus positives. Expert Opin. Drug Saf.,  2018, 17(3), 331-337.
[http://dx.doi.org/10.1080/14740338.2018.1433659] [PMID:  29415596] 
[32] 
Grünig, D.; Felser, A.; Duthaler, U.; Bouitbir, J.; Krähenbühl, S. Effect of the catechol-O-methyltransferase inhibitors tolcapone and entacapone on fatty acid metabolism in HepaRG cells. Toxicol. Sci.,  2018, 164(2), 477-488.
[http://dx.doi.org/10.1093/toxsci/kfy101] [PMID:  29688484] 
[33] 
Das, N.R.; Sharma, S.S.R.; Das, N.S.; Sharma, S. Cognitive impairment associated with parkinson’s disease: role of mitochondria. Curr. Neuropharmacol.,  2016, 14(6), 584-592.
[http://dx.doi.org/10.2174/1570159X14666160104142349] [PMID:  26725887] 
[34] 
Ferreira, J.J.; Lees, A.; Rocha, J-F.; Poewe, W.; Rascol, O.; Soares-da-Silva, P. Bi-Park 1 Investigators. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol.,  2016, 15(2), 154-165.
[http://dx.doi.org/10.1016/S1474-4422(15)00336-1] [PMID:  26725544] 
[35] 
Fallahi, S. Analysis of the effects of exercise on parkinson's
disease. B.S. Hons Thesis, the University of Arizona: Tuscan,
May 2017.
[36] 
Virmani, T.; Tazan, S.; Mazzoni, P.; Ford, B.; Greene, P.E. Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson’s disease. J. Clin. Mov. Disord.,  2016, 3, 8.
[http://dx.doi.org/10.1186/s40734-016-0036-9] [PMID:  27231577] 
[37] 
Siddique, Y.H.; Khan, W.; Fatima, A.; Jyoti, S.; Khanam, S.; Naz, F. Rahul; Ali, F.; Singh, B.R.; Naqvi, A.H. Effect of bromocriptine alginate nanocomposite (BANC) on a transgenic Drosophila model of Parkinson’s disease. Dis. Model. Mech.,  2016, 9(1), 63-68.
[http://dx.doi.org/10.1242/dmm.022145] [PMID:  26542705] 
[38] 
Jenner, P.; Katzenschlager, R. Apomorphine - pharmacological properties and clinical trials in Parkinson’s disease. Parkinsonism Relat. Disord.,  2016, 33(Suppl. 1), S13-S21.
[http://dx.doi.org/10.1016/j.parkreldis.2016.12.003] [PMID:  27979722] 
[39] 
Voon, V.; Napier, T.C.; Frank, M.J.; Sgambato-Faure, V.; Grace, A.A.; Rodriguez-Oroz, M.; Obeso, J.; Bezard, E.; Fernagut, P-O. Impulse control disorders and levodopa-induced dyskinesias in Parkinson’s disease: an update. Lancet Neurol.,  2017, 16(3), 238-250.
[http://dx.doi.org/10.1016/S1474-4422(17)30004-2] [PMID:  28229895] 
[40] 
You, H.; Mariani, L-L.; Mangone, G.; Le Febvre de Nailly, D.; Charbonnier-Beaupel, F.; Corvol, J-C. Molecular basis of dopamine replacement therapy and its side effects in Parkinson’s disease. Cell Tissue Res.,  2018, 373(1), 111-135.
[http://dx.doi.org/10.1007/s00441-018-2813-2] [PMID:  29516217] 
[41] 
Jiang, W.; Li, M.; He, F.; Bian, Z.; Liu, J.; He, Q.; Wang, X.; Sun, T.; Zhu, L. Dopamine D1 receptor agonist A-68930 inhibits NLRP3 inflammasome activation and protects rats from spinal cord injury-induced acute lung injury. Spinal Cord,  2016, 54(11), 951-956.
[http://dx.doi.org/10.1038/sc.2016.52] [PMID:  27067657] 
[42] 
Lizarraga, K.J.; Fox, S.H.; Strafella, A.P.; Lang, A.E. Hallucinations, delusions and impulse control disorders in Parkinson disease. Clin. Geriatr. Med.,  2020, 36(1), 105-118.
[http://dx.doi.org/10.1016/j.cger.2019.09.004] [PMID: 31733691] 
[43] 
Siddiqui, S.H.; Memon, N.A.; Shanker, R. Drug-induced movement disorder and confusion associated with duloxetine. BMJ Case Rep.,  2018, 2018, bcr2016216746.
[http://dx.doi.org/10.1136/bcr-2016-216746] [PMID:  29592972] 
[44] 
Kuo, B.; Singh, P. Nausea and vomiting related to the central nervous system diseases. In:Nausea and Vomiting; Koch, K.; Hasler, W., Eds.; Springer: Cham, 2017, pp. 109-118.
[http://dx.doi.org/10.1007/978-3-319-34076-0_8] 
[45] 
Zhang, P.; Li, Y.; Nie, K.; Wang, L.; Zhang, Y. Hypotension and bradycardia, a serious adverse effect of piribedil, a case report and literature review. BMC Neurol.,  2018, 18(1), 221.
[http://dx.doi.org/10.1186/s12883-018-1230-1] [PMID:  30591018] 
[46] 
Borovac, J.A. Side effects of a dopamine agonist therapy for Parkinson’s disease: a mini-review of clinical pharmacology. Yale J. Biol. Med.,  2016, 89(1), 37-47.
[PMID: 27505015] 
[47] 
Politi, C.; Ciccacci, C.; Novelli, G.; Borgiani, P. Genetics and treatment response in Parkinson’s disease: an update on pharmacogenetic studies. Neuromolecular Med.,  2018, 20(1), 1-17.
[http://dx.doi.org/10.1007/s12017-017-8473-7] [PMID:  29305687] 
[48] 
Inaba-Hasegawa, K.; Shamoto-Nagai, M.; Maruyama, W.; Naoi, M. Type B and A monoamine oxidase and their inhibitors regulate the gene expression of Bcl-2 and neurotrophic factors in human glioblastoma U118MG cells: different signal pathways for neuroprotection by selegiline and rasagiline. J. Neural Transm. (Vienna),  2017, 124(9), 1055-1066.
[http://dx.doi.org/10.1007/s00702-017-1740-9] [PMID:  28577058] 
[49] 
Finberg, J.P.; Rabey, J.M. Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front. Pharmacol.,  2016, 7, 340.
[http://dx.doi.org/10.3389/fphar.2016.00340] [PMID:  27803666] 
[50] 
Müller, T. Pharmacokinetics and pharmacodynamics of levodopa/carbidopa cotherapies for Parkinson’s disease. Expert Opin. Drug Metab. Toxicol.,  2020, 16(5), 403-414.
[http://dx.doi.org/10.1080/17425255.2020.1750596] [PMID:  32238065] 
[51] 
Sridhar, V.; Gaud, R.; Bajaj, A.; Wairkar, S. Pharmacokinetics and pharmacodynamics of intranasally administered selegiline nanoparticles with improved brain delivery in Parkinson’s disease. Nanomedicine (Lond.),  2018, 14(8), 2609-2618.
[http://dx.doi.org/10.1016/j.nano.2018.08.004] [PMID:  30171904] 
[52] 
Bundgaard, C.; Montezinho, L.P.; Anderson, N.; Thomsen, C.; Mørk, A. Selegiline induces a wake promoting effect in rats which is related to formation of its active metabolites. Pharmacol. Biochem. Behav.,  2016, 150-151, 147-152.
[http://dx.doi.org/10.1016/j.pbb.2016.10.003] [PMID:  27984094] 
[53] 
Hagenow, J.; Hagenow, S.; Grau, K.; Khanfar, M.; Hefke, L.; Proschak, E.; Stark, H. Reversible small molecule inhibitors of MAO A and MAO B with anilide motifs. Drug Des. Devel. Ther.,  2020, 14, 371-393.
[http://dx.doi.org/10.2147/DDDT.S236586] [PMID:  32099324] 
[54] 
Westerbeck, J.W.; Machamer, C.E. The infectious bronchitis coronavirus envelope protein alters Golgi pH to protect the spike protein and promote the release of infectious virus. J. Virol.,  2019, 93(11), e00015-e00019.
[http://dx.doi.org/10.1128/JVI.00015-19] [PMID:  30867314] 
[55] 
Aranda Abreu, G.E.; Hernández Aguilar, M.E.; Herrera Covarrubias, D.; Rojas Durán, F. Amantadine as a drug to mitigate the effects of COVID-19. Med. Hypotheses,  2020, 140, 109755.
[http://dx.doi.org/10.1016/j.mehy.2020.109755] [PMID:  32361100] 
[56] 
Olivola, S.; Xodo, S.; Olivola, E.; Cecchini, F.; Londero, A.P.; Driul, L. Parkinson’s disease in pregnancy: a case report and review of the literature. Front. Neurol.,  2020, 10, 1349.
[http://dx.doi.org/10.3389/fneur.2019.01349] [PMID:  32140133] 
[57] 
Nikolaus, S.; Wittsack, H-J.; Beu, M.; Antke, C.; Hautzel, H.; Wickrath, F.; Müller-Lutz, A.; De Souza Silva, M.A.; Huston, J.P.; Antoch, G.; Müller, H.W. Amantadine enhances nigrostriatal and mesolimbic dopamine function in the rat brain in relation to motor and exploratory activity. Pharmacol. Biochem. Behav.,  2019, 179, 156-170.
[http://dx.doi.org/10.1016/j.pbb.2018.12.010] [PMID:  30639878] 
[58] 
Fryml, L.D.; Williams, K.R.; Pelic, C.G.; Fox, J.; Sahlem, G.; Robert, S.; Revuelta, G.J.; Short, E.B. The role of amantadine withdrawal in 3 cases of treatment-refractory altered mental status. J. Psychiatr. Pract.,  2017, 23(3), 191-199.
[http://dx.doi.org/10.1097/PRA.0000000000000237] [PMID:  28492457] 
[59] 
Oertel, W.; Eggert, K.; Pahwa, R.; Tanner, C.M.; Hauser, R.A.; Trenkwalder, C.; Ehret, R.; Azulay, J.P.; Isaacson, S.; Felt, L.; Stempien, M.J. Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in parkinson’s disease (EASE LID 3). Mov. Disord.,  2017, 32(12), 1701-1709.
[http://dx.doi.org/10.1002/mds.27131] [PMID:  28833562] 
[60] 
Yiğit, U.; Erdenöz, S.; Uslu, U.; Oba, E.; Cumbul, A.; Cağatay, H.; Aktaş, S.; Eskicoğlu, E. An immunohistochemical analysis of the neuroprotective effects of memantine, hyperbaric oxygen therapy, and brimonidine after acute ischemia reperfusion injury. Mol. Vis.,  2011, 17, 1024-1033.
[PMID: 21541269] 
[61] 
Parker, C. Psychiatric effects of drugs for other disorders. Treat. Strat. Psychopharmacol.,  2016, 44(12), 768-774.
[http://dx.doi.org/10.1016/j.mpmed.2016.09.011] 
[62] 
Crispo, J.A.G.; Willis, A.W.; Thibault, D.P.; Fortin, Y.; Emons, M.; Bjerre, L.M.; Kohen, D.E.; Perez-Lloret, S.; Mattison, D.; Krewski, D. Associations between cardiovascular events and nonergot dopamine agonists in parkinson’s disease. Mov. Disord. Clin. Pract.,  2015, 3(3), 257-267.
[http://dx.doi.org/10.1002/mdc3.12286] [PMID:  30363519] 
[63] 
Kim, H.J.; Jeon, B.S.; Jenner, P. Hallmarks of treatment aspects: Parkinson’s disease throughout centuries including l-Dopa. Int. Rev. Neurobiol.,  2017, 132, 295-343.
[http://dx.doi.org/10.1016/bs.irn.2017.01.006] [PMID: 28554412] 
[64] 
Nishtala, P.S.; Salahudeen, M.S.; Hilmer, S.N. Anticholinergics: theoretical and clinical overview. Expert Opin. Drug Saf.,  2016, 15(6), 753-768.
[http://dx.doi.org/10.1517/14740338.2016.1165664] [PMID:  26966981] 
[65] 
Eastman, R.T.; Roth, J.S.; Brimacombe, K.R.; Simeonov, A.; Shen, M.; Patnaik, S.; Hall, M.D. Remdesivir: a review of its discovery and development leading to human clinical trials for treatment of COVID-19. ACS Cent. Sci.,  2020, 6(6), 1009.
[http://dx.doi.org/10.1021/acscentsci.0c00747] [PMID: 32607448] 
[66] 
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; Ray, A.S.; Cihlar, T.; Siegel, D.; Mackman, R.L.O.; Clarke, M.; Baric, R.S.; Denison, M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio,  2018, 9(12), e00221-e18.
[http://dx.doi.org/10.1128/mbio.00221-18] [PMID:  29511076] 
[67] 
Gordon, C.J.; Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Götte, M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J. Biol. Chem.,  2020, 295(15), 4773-4779.
[http://dx.doi.org/10.1074/jbc.AC120.013056] [PMID:  32094225] 
[68] 
Yin, W.; Mao, C.; Luan, X.; Shen, D-D.; Shen, Q.; Su, H.; Wang, X.; Zhou, F.; Zhao, W.; Gao, M.; Chang, S.; Xie, Y.C.; Tian, G.; Jiang, H.W.; Tao, S.C.; Shen, J.; Jiang, Y.; Jiang, H.; Xu, Y.; Zhang, S.; Zhang, Y.; Xu, H.E. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science,  2020, 368(6498), 1499-1504.
[http://dx.doi.org/10.1126/science.abc1560] [PMID:  32358203] 
[69] 
de Wit, E.; Feldmann, F.; Cronin, J.; Jordan, R.; Okumura, A.; Thomas, T.; Scott, D.; Cihlar, T.; Feldmann, H. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc. Natl. Acad. Sci. USA,  2020, 117(12), 6771-6776.
[http://dx.doi.org/10.1073/pnas.1922083117] [PMID:  32054787] 
[70] 
Al-Tawfiq, J.A.; Al-Homoud, A.H.; Memish, Z.A. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med. Infect. Dis.,  2020, 34, 101615.
[http://dx.doi.org/10.1016/j.tmaid.2020.101615] [PMID:  32145386] 
[71] 
Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; Spahn, J.E.; Bauer, L.; Sellers, S.; Porter, D.; Feng, J.Y.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun.,  2020, 11(1), 222.
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID:  31924756] 
[72] 
Lo, M.K.; Feldmann, F.; Gary, J.M.; Jordan, R.; Bannister, R.; Cronin, J.; Patel, N.R.; Klena, J.D.; Nichol, S.T.; Cihlar, T.; Zaki, S.R.; Feldmann, H.; Spiropoulou, C.F.; de Wit, E. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci. Transl. Med.,  2019, 11(494), eaau9242.
[http://dx.doi.org/10.1126/scitranslmed.aau9242] [PMID:  31142680] 
[73] 
Grein, J.; Ohmagari, N.; Shin, D.; Diaz, G.; Asperges, E.; Castagna, A.; Feldt, T.; Green, G.; Green, M.L.; Lescure, F-X.; Nicastri, E.; Oda, R.; Yo, K.; Quiros-Roldan, E.; Studemeister, A.; Redinski, J.; Ahmed, S.; Bernett, J.; Chelliah, D.; Chen, D.; Chihara, S.; Cohen, S.H.; Cunningham, J.; D’Arminio Monforte, A.; Ismail, S.; Kato, H.; Lapadula, G.; L’Her, E.; Maeno, T.; Majumder, S.; Massari, M.; Mora-Rillo, M.; Mutoh, Y.; Nguyen, D.; Verweij, E.; Zoufaly, A.; Osinusi, A.O.; DeZure, A.; Zhao, Y.; Zhong, L.; Chokkalingam, A.; Elboudwarej, E.; Telep, L.; Timbs, L.; Henne, I.; Sellers, S.; Cao, H.; Tan, S.K.; Winterbourne, L.; Desai, P.; Mera, R.; Gaggar, A.; Myers, R.P.; Brainard, D.M.; Childs, R.; Flanigan, T. Compassionate use of remdesivir for patients with severe Covid-19. N. Engl. J. Med.,  2020, 382(24), 2327-2336.
[http://dx.doi.org/10.1056/NEJMoa2007016] [PMID:  32275812] 
[74] 
Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA, 2020.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID:  32282022] 
[75] 
Holt, N.R.; Neumann, J.T.; McNeil, J.J.; Cheng, A.C.; Unit, H.E.; Prahan, V. Implications of COVID-19 in an ageing population. Med. J. Aust.,  2020, 213(8), 342-344.e1.
[http://dx.doi.org/10.5694/mja2.50785] [PMID:  32946607] 
[76] 
Furuta, Y.; Komeno, T.; Nakamura, T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci.,  2017, 93(7), 449-463.
[http://dx.doi.org/10.2183/pjab.93.027] [PMID:  28769016] 
[77] 
Deval, J.; Jin, Z.; Chuang, Y-C.; Kao, C.C. Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses. Virus Res.,  2017, 234, 21-33.
[http://dx.doi.org/10.1016/j.virusres.2016.12.018] [PMID:  28041960] 
[78] 
Westover, J.B.; Sefing, E.J.; Bailey, K.W.; Van Wettere, A.J.; Jung, K-H.; Dagley, A.; Wandersee, L.; Downs, B.; Smee, D.F.; Furuta, Y.; Bray, M.; Gowen, B.B. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses. Antiviral Res.,  2016, 126, 62-68.
[http://dx.doi.org/10.1016/j.antiviral.2015.12.006] [PMID:  26711718] 
[79] 
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res.,  2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID:  32020029] 
[80] 
Shiraki, K.; Daikoku, T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol. Ther.,  2020, 209, 107512.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107512] [PMID:  32097670] 
[81] 
Guan, W-J.; Ni, Z-Y.; Hu, Y.; Liang, W-H.; Ou, C-Q.; He, J-X.; Liu, L.; Shan, H.; Lei, C-L.; Hui, D.S.C.; Du, B.; Li, L.J.; Zeng, G.; Yuen, K.Y.; Chen, R.C.; Tang, C.L.; Wang, T.; Chen, P.Y.; Xiang, J.; Li, S.Y.; Wang, J.L.; Liang, Z.J.; Peng, Y.X.; Wei, L.; Liu, Y.; Hu, Y.H.; Peng, P.; Wang, J.M.; Liu, J.Y.; Chen, Z.; Li, G.; Zheng, Z.J.; Qiu, S.Q.; Luo, J.; Ye, C.J.; Zhu, S.Y.; Zhong, N.S. China Medical Treatment Expert Group for Covid-19. Clinical characteristics of 2019 novel coronavirus infection in China. N. Engl. J. Med.,  2020, 382(18), 1708-1720.
[http://dx.doi.org/10.1056/nejmoa2002032] [PMID: 32109013] 
[82] 
Zhao, Y.; Harmatz, J.S.; Epstein, C.R.; Nakagawa, Y.; Kurosaki, C.; Nakamura, T.; Kadota, T.; Giesing, D.; Court, M.H.; Greenblatt, D.J. Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen. Br. J. Clin. Pharmacol.,  2015, 80(5), 1076-1085.
[http://dx.doi.org/10.1111/bcp.12644] [PMID:  25808818] 
[83] 
Du, Y.X.; Chen, X.P. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019‐nCoV infection. Clin. Pharmacol. Ther.,  2020, 108(2), 242-247.
[http://dx.doi.org/10.1002/cpt.1844] [PMID:  32246834] 
[84] 
Colson, P.; Rolain, J-M.; Lagier, J-C.; Brouqui, P.; Raoult, D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int. J. Antimicrob. Agents,  2020, 55(4), 105932.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105932] [PMID:  32145363] 
[85] 
Mahase, E. Covid-19: 146 researchers raise concerns over chloroquine study that halted WHO trial. BMJ,  2020, 369, m2197.
[http://dx.doi.org/10.1136/bmj.m2197] [PMID: 32487664] 
[86] 
Mehra, M.R.; Desai, S.S.; Ruschitzka, F.; Patel, A.N. Hydroxychloroquine
or chloroquine with or without a macrolide
for treatment of COVID-19: a multinational registry
analysis. Lancet, 2020. S0140-6736(20)31180-6.
[http://dx.doi.org/10.1016/s0140-6736(20)31180-6] [PMID: 32450107] 
[87] 
Principi, N.; Esposito, S. Chloroquine or hydroxychloroquine for prophylaxis of COVID-19. Lancet Infect. Dis.,  2020, 20(10), 1118.
[http://dx.doi.org/10.1016/s1473-3099(20)30296-6] [PMID: 32311322] 
[88] 
Schrezenmeier, E.; Dörner, T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat. Rev. Rheumatol.,  2020, 16(3), 155-166.
[http://dx.doi.org/10.1038/s41584-020-0372-x] [PMID:  32034323] 
[89] 
Naveau, T.; Lichau, O.; Barnetche, T.; Blanco, P.; Truchetet, M-E.; Richez, C. O7 Safety of chloroquine and hydroxychloroquine during pregnancy: a systematic literature review and meta-analysis. Lupus Sci. Med.,  2020, 7(Suppl. 1), A10.
[http://dx.doi.org/10.1136/lupus-2020-eurolupus.20] 
[90] 
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), 72-73.
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID:  32074550] 
[91] 
Chen, J.; Liu, D.; Liu, L.; Liu, P. Xu. Q.;Xia, L.; Ling, Y.; Huang, D.; Song, S.; Zhang, D.; Qian, Z.; Li, T.; Shen, Y.; Lu, H. [A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)]. Zhejiang Da Xue Xue Bao Yi Xue Ban,  2020, 49(2), 215-219.
[http://dx.doi.org/10.3785/j.issn.1008-9292.2020.03.03] [PMID: 32391667] 
[92] 
Fedele, A.O.; Proud, C.G. Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling. Biosci. Rep.,  2020, 40(4), 40.
[http://dx.doi.org/10.1042/BSR20200905] [PMID:  32285908] 
[93] 
Fantini, J.; Di Scala, C.; Chahinian, H.; Yahi, N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int. J. Antimicrob. Agents,  2020, 55(5), 105960.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105960] [PMID:  32251731] 
[94] 
Hu, T.Y.; Frieman, M.; Wolfram, J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat. Nanotechnol.,  2020, 15(4), 247-249.
[http://dx.doi.org/10.1038/s41565-020-0674-9] [PMID:  32203437] 
[95] 
Zhao, M. Cytokine storm and immunomodulatory therapy in COVID-19: role of chloroquine and anti-IL-6 monoclonal antibodies. Int. J. Antimicrob. Agents,  2020, 55(6), 105982.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105982] [PMID:  32305588] 
[96] 
Tsubone, T.M.; de Sousa Rocha, C.; Tonolli, P.N. In vitro autophagy modulation with chloroquine some lessons to learn. Adv. Biochem. Biotech.,  2020, 5, 1098.
[http://dx.doi.org/10.29011/2574-7258.001098] 
[97] 
Yao, X.; Ye, F.; Zhang, M.; Cui, C.; Huang, B.; Niu, P.; Liu, X.; Zhao, L.; Dong, E.; Song, C.; Zhan, S.; Lu, R.; Li, H.; Tan, W.; Liu, D. 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, 71(15), 732-739.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID:  32150618] 
[98] 
Plantone, D.; Koudriavtseva, T. Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review. Clin. Drug Investig.,  2018, 38(8), 653-671.
[http://dx.doi.org/10.1007/s40261-018-0656-y] [PMID:  29737455] 
[99] 
Leonard, A.; Möhlis, K.; Schlüter, R.; Taylor, E.; Lalk, M.; Methling, K. Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics. J. Antibiot. (Tokyo),  2020, 73(7), 441-454.
[http://dx.doi.org/10.1038/s41429-020-0296-3] [PMID:  32210362] 
[100] 
Molina, J.M.; Delaugerre, C.; Le Goff, J.; Mela-Lima, B.; Ponscarme, D.; Goldwirt, L.; de Castro, N. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med. Mal. Infect.,  2020, 50(4), 384.
[http://dx.doi.org/10.1016/j.medmal.2020.03.006] [PMID:  32240719] 
[101] 
Romano, S.S.; Jensen, J.S.; Lowens, M.S.; Morgan, J.L.; Chambers, L.C.; Robinson, T.S.; Totten, P.A.; Soge, O.O.; Golden, M.R.; Manhart, L.E. Long duration of asymptomatic Mycoplasma genitalium infection after syndromic treatment for nongonococcal urethritis. Clin. Infect. Dis.,  2019, 69(1), 113-120.
[http://dx.doi.org/10.1093/cid/ciy843] [PMID:  30281079] 
[102] 
Mercorelli, B.; Palù, G.; Loregian, A. Drug repurposing for viral infectious diseases: how far are we? Trends Microbiol.,  2018, 26(10), 865-876.
[http://dx.doi.org/10.1016/j.tim.2018.04.004] [PMID:  29759926] 
[103] 
Bosseboeuf, E.; Aubry, M.; Nhan, T.; de Pina, J.J.; Rolain, J.M.; Raoult, D.; Musso, D. Azithromycin Inhibits the Replication of Zika Virus. J. Antivir. Antiretrovir.,  2018, 10(1), 6-11.
[http://dx.doi.org/10.4172/1948-5964.1000173] 
[104] 
Vega-Briceño, L.E.; Sánchez, I. Pulmonary anti-inflammatory effects of macrolides. In:Pediatric Respiratory Diseases; Bertrand, P.; Sánchez, I., Eds.; Springer: New York, 2020, Vol. 1, pp. 643-648.
[http://dx.doi.org/10.1007/978-3-030-26961-6_62] 
[105] 
Gérard, A.; Romani, S.; Fresse, A.; Viard, D.; Parassol, N.; Granvuillemin, A.; Chouchana, L.; Rocher, F.; Drici, M-D. French Network of Pharmacovigilance Centers. “Off-label” use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French network of pharmacovigilance centers. Therapie,  2020, 75(4), 371-379.
[http://dx.doi.org/10.1016/j.therap.2020.05.002] [PMID: 32418730] 
[106] 
Sargiacomo, C.; Sotgia, F.; Lisanti, M.P. COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging (Albany NY),  2020, 12(8), 6511-6517.
[http://dx.doi.org/10.18632/aging.103001] [PMID:  32229706] 
[107] 
Naiel, S.; Tat, V.; Padwal, M.; Vierhout, M.; Mekhael, O.; Yousof, T.; Ayoub, A.; Abed, S.; Dvorkin-Gheva, A.; Ask, K. Protein misfolding and endoplasmic reticulum stress in chronic lung disease: will cell-specific targeting be the key to the cure? Chest,  2020, 157(5), 1207-1220.
[http://dx.doi.org/10.1016/j.chest.2019.11.009] [PMID:  31778676] 
[108] 
Song, S.; Lam, E.W-F.; Tchkonia, T.; Kirkland, J.L.; Sun, Y. Senescent cells: emerging targets for human aging and age-related diseases. Trends Biochem. Sci.,  2020, 45(7), 578-592.
[http://dx.doi.org/10.1016/j.tibs.2020.03.008] [PMID:  32531228] 
[109] 
Pellegrini, C.; Ippolito, C.; Segnani, C.; Dolfi, A.; Errede, M.; Virgintino, D.; Fornai, M.; Antonioli, L.; Garelli, F.; Nericcio, A.; Colucci, R.; Cerri, S.; Blandini, F.; Blandizzi, C.; Bernardini, N. Pathological remodelling of colonic wall following dopaminergic nigrostriatal neurodegeneration. Neurobiol. Dis.,  2020, 139, 104821.
[http://dx.doi.org/10.1016/j.nbd.2020.104821] [PMID:  32088380] 
[110] 
Mitha, E.; Krivan, G.; Jacobs, F.; Nagler, A.; Alrabaa, S.; Mykietiuk, A.; Kenwright, A.; Le Pogam, S.; Clinch, B.; Vareikiene, L. Safety, resistance, and efficacy results from a phase IIIb study of conventional-and double-dose oseltamivir regimens for treatment of influenza in immunocompromised patients. Infect. Dis. Ther.,  2019, 8(4), 613-626.
[http://dx.doi.org/10.1007/s40121-019-00271-8] [PMID:  31667696] 
[111] 
Ju, H.; Zhang, J.; Sun, Z.; Huang, Z.; Qi, W.; Huang, B.; Zhan, P.; Liu, X. Discovery of C-1 modified oseltamivir derivatives as potent influenza neuraminidase inhibitors. Eur. J. Med. Chem.,  2018, 146, 220-231.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.050] [PMID:  29407952] 
[112] 
Belhadi, D.; Peiffer-Smadja, N.; Lescure, F.-X.; Yazdanpanah, Y.; Mentré, F.; Laouénan, C. A brief review of antiviral
drugs evaluated in registered clinical trials for COVID-
19. medRxiv, 2020. preprint
[http://dx.doi.org/10.1101/2020.03.18.20038190] 
[113] 
Rosa, S.G.V.; Santos, W.C. Clinical trials on drug repositioning for COVID-19 treatment. Rev. Panam. Salud Publica,  2020, 44, e40.
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID:  32256547] 
[114] 
Matsuzono, K.; Baba, M.; Imai, G.; Imai, H.; Fujimoto, S. Malignant syndrome triggered by influenza A virus infection in a patient with Parkinson’s disease with improvement after intravenous peramivir treatment. Neurol. Sci.,  2019, 40(6), 1291-1294.
[http://dx.doi.org/10.1007/s10072-018-3696-4] [PMID:  30617448] 
[115] 
Chen, Y.W.; Yiu, C.B.; Wong, K-Y. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000 Res.,  2020, 9, 129.
[http://dx.doi.org/10.12688/f1000research.22457.2] [PMID:  32194944] 
[116] 
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med.,  2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID:  32187464] 
[117] 
Wu, C.; Chen, X.; Cai, Y.; Xia, J.; Zhou, X.; Xu, S.; Huang, H.; Zhang, L.; Zhou, X.; Du, C.; Zhang, Y.; Song, J.; Wang, S.; Chao, Y.; Yang, Z.; Xu, J.; Zhou, X.; Chen, D.; Xiong, W.; Xu, L.; Zhou, F.; Jiang, J.; Bai, C.; Zheng, J.; Song, Y. Risk factors associated with acute respiratory distress syndrome
and death in patients with coronavirus disease 2019
pneumonia in Wuhan, China. JAMA Intern. Med, 2020.
[http://dx.doi.org/10.1001/jamainternmed.2020.0994] [PMID: 32167524] 
[118] 
Longo, D.M.; Yang, Y.; Watkins, P.B.; Howell, B.A.; Siler, S.Q. Elucidating differences in the hepatotoxic potential of tolcapone and entacapone with DILIsym®, a mechanistic model of drug‐induced liver injury. CPT Pharmacometrics Syst. Pharmacol.,  2016, 5(1), 31-39.
[http://dx.doi.org/10.1002/psp4.12053] [PMID:  26844013] 
[119] 
Kadam, R.U.; Wilson, I.A. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc. Natl. Acad. Sci. USA,  2017, 114(2), 206-214.
[http://dx.doi.org/10.1073/pnas.1617020114] [PMID:  28003465] 
[120] 
Ahsan, W.; Javed, S.; Bratty, M.A.; Alhazmi, H.A.; Najmi, A. Treatment of SARS-CoV-2: How far have we reached? Drug Discov. Ther.,  2020, 14(2), 67-72.
[http://dx.doi.org/10.5582/ddt.2020.03008] [PMID:  32336723] 
[121] 
Zhang, J.; Zhou, L.; Yang, Y.; Peng, W.; Wang, W.; Chen, X. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet Respir. Med.,  2020, 8(3), e11-e12.
[http://dx.doi.org/10.1016/S2213-2600(20)30071-0] [PMID:  32061335] 
[122] 
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet,  2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID:  31986264] 
[123] 
Li, X.; Xu, S.; Yu, M.; Wang, K.; Tao, Y.; Zhou, Y.; Shi, J.; Zhou, M.; Wu, B.; Yang, Z.; Zhang, C.; Yue, J.; Zhang, Z.; Renz, H.; Liu, X.; Xie, J.; Xie, M.; Zhao, J. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J. Allergy Clin. Immunol.,  2020, 146(1), 110-118.
[http://dx.doi.org/10.1016/j.jaci.2020.04.006] [PMID:  32294485] 
[124] 
Liu, B.; Li, M.; Zhou, Z.; Guan, X.; Xiang, Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J. Autoimmun.,  2020, 111, 102452.
[http://dx.doi.org/10.1016/j.jaut.2020.102452] [PMID:  32291137] 
[125] 
Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; Guan, L.; Wei, Y.; Li, H.; Wu, X.; Xu, J.; Tu, S.; Zhang, Y.; Chen, H.; Cao, B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet,  2020, 395(10229), 1054-1062.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID:  32171076] 
[126] 
Konig, M.F.; Powell, M.; Staedtke, V.; Bai, R-Y.; Thomas, D.L.; Fischer, N.; Huq, S.; Khalafallah, A.M.; Koenecke, A.; Xiong, R.; Mensh, B.; Papadopoulos, N.; Kinzler, K.W.; Vogelstein, B.; Vogelstein, J.T.; Athey, S.; Zhou, S.; Bettegowda, C. Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists. J. Clin. Invest.,  2020, 130(7), 3345-3347.
[http://dx.doi.org/10.1172/JCI139642] [PMID:  32352407] 
[127] 
Lythgoe, M.P.; Middleton, P. Ongoing clinical trials for the management of the COVID-19 pandemic. Trends Pharmacol. Sci.,  2020, 41(6), 363-382.
[http://dx.doi.org/10.1016/j.tips.2020.03.006] [PMID:  32291112] 
[128] 
Kannoth, S.; Anandakkuttan, A.; Mathai, A.; Sasikumar, A.N.; Nambiar, V. Autoimmune atypical parkinsonism - A group of treatable parkinsonism. J. Neurol. Sci.,  2016, 362, 40-46.
[http://dx.doi.org/10.1016/j.jns.2016.01.006] [PMID:  26944115] 
[129] 
Shen, C.; Wang, Z.; Zhao, F.; Yang, Y.; Li, J.; Yuan, J.; Wang, F.; Li, D.; Yang, M.; Xing, L.; Wei, J.; Xiao, H.; Yang, Y.; Qu, J.; Qing, L.; Chen, L.; Xu, Z.; Peng, L.; Li, Y.; Zheng, H.; Chen, F.; Huang, K.; Jiang, Y.; Liu, D.; Zhang, Z.; Liu, Y.; Liu, L. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA,  2020, 323, 1582-1589.
[http://dx.doi.org/10.1001/jama.2020.4783] [PMID:  32219428] 
[130] 
Arabi, Y.M.; Hajeer, A.H.; Luke, T.; Raviprakash, K.; Balkhy, H.; Johani, S.; Al-Dawood, A.; Al-Qahtani, S.; Al-Omari, A.; Al-Hameed, F.; Hayden, F.G.; Fowler, R.; Bouchama, A.; Shindo, N.; Al-Khairy, K.; Carson, G.; Taha, Y.; Sadat, M.; Alahmadi, M. Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia. Emerg. Infect. Dis.,  2016, 22(9), 1554-1561.
[http://dx.doi.org/10.3201/eid2209.151164] [PMID:  27532807] 
[131] 
Chen, L.; Xiong, J.; Bao, L.; Shi, Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect. Dis.,  2020, 20(4), 398-400.
[http://dx.doi.org/10.1016/S1473-3099(20)30141-9] [PMID:  32113510] 
[132] 
Mair-Jenkins, J.; Saavedra-Campos, M.; Baillie, J.K.; Cleary, P.; Khaw, F-M.; Lim, W.S.; Makki, S.; Rooney, K.D.; Nguyen-Van-Tam, J.S.; Beck, C.R. Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J. Infect. Dis.,  2015, 211(1), 80-90.
[http://dx.doi.org/10.1093/infdis/jiu396] [PMID:  25030060] 
[133] 
Jankovic, J. Immunologic treatment of Parkinson’s disease. Immunotherapy,  2018, 10(2), 81-84.
[http://dx.doi.org/10.2217/imt-2017-0146] [PMID:  29260621] 
[134] 
Nisar, T.; Sutherland-Foggio, H.; Husar, W. Antiviral amantadine. Lancet Neurol.,  2019, 18(12), 1080.
[http://dx.doi.org/10.1016/S1474-4422(19)30361-8] [PMID:  31973807] 
[135] 
Dey, D.; Siddiqui, S.I.; Mamidi, P.; Ghosh, S.; Kumar, C.S.; Chattopadhyay, S.; Ghosh, S.; Banerjee, M. The effect of amantadine on an ion channel protein from Chikungunya virus. PLoS Negl. Trop. Dis.,  2019, 13(7), e0007548.
[http://dx.doi.org/10.1371/journal.pntd.0007548] [PMID:  31339886] 
[136] 
Rejdak, K.; Grieb, P. Adamantanes might be protective from COVID-19 in patients with neurological diseases: multiple sclerosis, parkinsonism and cognitive impairment. Mult. Scler. Relat. Disord.,  2020, 42, 102163.
[http://dx.doi.org/10.1016/j.msard.2020.102163] [PMID:  32388458] 
[137] 
Smieszek, S.; Przychodzen, B.; Polymeropoulos, M.H. Amantadine disrupts lysosomal gene expression; potential therapy for COVID19. bioRxiv, 2020. preprint.
[http://dx.doi.org/10.1101/2020.04.05.026187] 
[138] 
Hill, A.T.; Gold, P.M.; El Solh, A.A.; Metlay, J.P.; Ireland, B.; Irwin, R.S.; Adams, T.M.; Altman, K.W.; Azoulay, E.; Barker, A.F. CHEST Expert Cough Panel. Adult outpatients with acute cough due to suspected pneumonia or influenza: CHEST guideline and expert panel report. Chest,  2019, 155(1), 155-167.
[http://dx.doi.org/10.1016/j.chest.2018.09.016] [PMID:  30296418] 
[139] 
Choi, J-G.; Kim, Y.S.; Kim, J.H.; Chung, H-S. Antiviral activity of ethanol extract of Geranii Herba and its components against influenza viruses via neuraminidase inhibition. Sci. Rep.,  2019, 9(1), 12132.
[http://dx.doi.org/10.1038/s41598-019-48430-8] [PMID:  31431635] 
[140] 
Cimolai, N. Potentially repurposing adamantanes for COVID-19. J. Med. Virol.,  2020, 92(6), 531-532.
[http://dx.doi.org/10.1002/jmv.25752] [PMID:  32176361] 
[141] 
Choy, K-T.; Wong, A.Y-L.; Kaewpreedee, P.; Sia, S-F.; Chen, D.; Hui, K.P.Y.; Chu, D.K.W.; Chan, M.C.W.; Cheung, P.P-H.; Huang, X.; Peiris, M.; Yen, H.L. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res.,  2020, 178, 104786.
[http://dx.doi.org/10.1016/j.antiviral.2020.104786] [PMID:  32251767] 
[142] 
Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Götte, M. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses,  2019, 11(4), 326.
[http://dx.doi.org/10.3390/v11040326] [PMID:  30987343] 
[143] 
Jean, S-S.; Lee, P-I.; Hsueh, P-R. Treatment options for COVID-19: the reality and challenges. J. Microbiol. Immunol. Infect.,  2020, 53(3), 436-443.
[http://dx.doi.org/10.1016/j.jmii.2020.03.034] [PMID:  32307245] 
[144] 
Varga, A.; Lionne, C.; Roy, B. Intracellular metabolism of nucleoside/nucleotide analogues: a bottleneck to reach active drugs on HIV reverse transcriptase. Curr. Drug Metab.,  2016, 17(3), 237-252.
[http://dx.doi.org/10.2174/1389200217666151210141903] [PMID:  26651972] 
[145] 
Abena, P.M.; Decloedt, E.H.; Bottieau, E.; Suleman, F.; Adejumo, P.; Sam-Agudu, N.A. Muyembe TamFum J-J, Seydi M, Eholie SP, Mills EJ. Chloroquine and hydroxychloroquine for the prevention or treatment of (COVID-19) in Africa: caution for inappropriate off-label use in healthcare settings. Am. J. Trop. Med. Hyg.,  2020, 102(6), 1184-1188.
[http://dx.doi.org/10.4269/ajtmh.20-0290]] [PMID:  32323646] 
[146] 
Sahoo, S.; Kumar, M.; Sinha, V.K. Chloroquine-induced recurrent psychosis. Am. J. Ther.,  2007, 14(4), 406-407.
[http://dx.doi.org/10.1097/MJT.0b013e31802e4b0e] [PMID:  17667217] 
[147] 
Dahly, D; Gates, S; Morris, T Statistical review of hydroxychloroquine
and azithromycin as a treatment of
COVID-19: results of an open-label nonrandomized clinical
trial. Zonodo.org, 2020. preprint.
[http://dx.doi.org/10.5281/zenodo.3724166] 
[148] 
Gautret, P.; Lagier, J-C.; Parola, P.; Hoang, V.T.; Meddeb, L.; Mailhe, M.; Doudier, B.; Courjon, J.; Giordanengo, V.; Vieira, V.E.; Tissot Dupont, H.; Honoré, S.; Colson, P.; Chabrière, E.; La Scola, B.; Rolain, J.M.; Brouqui, P.; Raoult, D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents,  2020, 56(1), 105949.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID:  32205204] 
[149] 
Ramadhani, A.M.; Derrick, T.; Macleod, D.; Massae, P.; Malisa, A.; Mbuya, K.; Mtuy, T.; Makupa, W.; Roberts, C.H.; Bailey, R.L.; Mabey, D.C.W.; Holland, M.J.; Burton, M.J. Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community. PLoS Negl. Trop. Dis.,  2019, 13(7), e0007559.
[http://dx.doi.org/10.1371/journal.pntd.0007559] [PMID:  31306419] 
[150] 
Rascol, O.; Negre-Pages, L.; Damier, P.; Delval, A.; Derkinderen, P.; Destée, A.; Fabbri, M.; Meissner, W.G.; Rachdi, A.; Tison, F.; Perez-Lloret, S. COPARK Study Group. Utilization patterns of amantadine in parkinson’s disease patients enrolled in the French COPARK Study. Drugs Aging,  2020, 37(3), 215-223.
[http://dx.doi.org/10.1007/s40266-019-00740-2] [PMID:  31919803] 
[151] 
Kode, S.S.; Pawar, S.D.; Tare, D.S.; Keng, S.S.; Mullick, J. Amantadine resistance markers among low pathogenic avian influenza H9N2 viruses isolated from poultry in India, during 2009-2017. Microb. Pathog.,  2019, 137, 103779.
[http://dx.doi.org/10.1016/j.micpath.2019.103779] [PMID:  31600542] 
[152] 
Ying, B.; Pang, S.; Yang, J.; Zhong, Y.; Wang, J. Computational study of HCV p7 channel: insight into a new strategy for HCV inhibitor design. Interdiscip. Sci.,  2019, 11(2), 292-299.
[http://dx.doi.org/10.1007/s12539-018-0306-3] [PMID:  30194627] 
[153] 
Mazzon, M.; Marsh, M. Targeting viral entry as a strategy
for broad-spectrum antivirals. F1000 Res,  2019, 8 F1000 Faculty Rev-1628.
[http://dx.doi.org/10.12688/f1000research.19694.1] [PMID: 31559009] 
[154] 
Smieszek, S.P.; Przychodzen, B.P.; Polymeropoulos, M.H. Amantadine disrupts lysosomal gene expression: a hypothesis for COVID19 treatment. Int. J. Antimicrob. Agents,  2020, 55(6), 106004.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106004] [PMID:  32361028] 
[155] 
Helmich, R.C.; Bloem, B.R. The impact of the COVID-19 pandemic on Parkinson’s disease: hidden sorrows and emerging opportunities. J. Parkinsons Dis.,  2020, 10(2), 351-354.
[http://dx.doi.org/10.3233/JPD-202038] [PMID:  32250324] 
[156] 
Gilat, M.; Ehgoetz Martens, K.A.; Miranda-Domínguez, O.; Arpan, I.; Shine, J.M.; Mancini, M.; Fair, D.A.; Lewis, S.J.G.; Horak, F.B. Dysfunctional limbic circuitry underlying freezing of gait in Parkinson’s disease. Neuroscience,  2018, 374, 119-132.
[http://dx.doi.org/10.1016/j.neuroscience.2018.01.044] [PMID:  29408498] 
Rights & Permissions Print Cite
Article Metrics
49
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867327666200903115138	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Targeting COVID-19 in Parkinson’s Patients: Drugs Repurposed

Abstract Play Pause

Related Journals

Related Books

Related Articles

Abstract
