Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Repurposed Antiviral Drugs for the Treatment of COVID-19: Syntheses, Mechanism of Infection and Clinical Trials

Author(s): Subha Sankar Paul and Goutam Biswas*

Volume 21, Issue 9, 2021

Published on: 22 December, 2020

Page: [1123 - 1143] Pages: 21

DOI: 10.2174/1389557521666201222145842

Price: $65

Abstract

COVID-19 is a public health emergency of international concern. Although considerable knowledge has been acquired with time about the viral mechanism of infection and mode of replication, yet no specific drugs or vaccines have been discovered against SARS-CoV-2 to date. There are few small molecule antiviral drugs like Remdesivir and Favipiravir, which have shown promising results in different advanced stages of clinical trials. Chloroquinine, Hydroxychloroquine, and Lopinavir- Ritonavir combination, although initially were hypothesized to be effective against SARSCoV- 2, are now discontinued from the solidarity clinical trials. This review provides a brief description of their chemical syntheses along with their mode of action, and clinical trial results available on Google and in different peer-reviewed journals till 24th October 2020.

Keywords: SARS-CoV-2, coronavirus, antiviral drugs, repurposed drugs, remdesivir, synthesis.

Graphical Abstract
[1]
Wu, F.; Zhao, S.; Yu, B.; Chen, Y.M.; Wang, W.; Song, Z.G.; Hu, Y.; Tao, Z.W.; Tian, J.H.; Pei, Y.Y.; Yuan, M.L.; Zhang, Y.L.; Dai, F.H.; Liu, Y.; Wang, Q.M.; Zheng, J.J.; Xu, L.; Holmes, E.C.; Zhang, Y.Z. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798), 265-269.
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[2]
WHO Coronavirus Disease (COVID-19) Dashboard., https://covid19.who.int
[3]
Ioannidis, J. The infection fatality rate of COVID-19 inferred from seroprevalence data. Bull. World Health Organ., 2021, 99, 19-33F.
[http://dx.doi.org/10.1101/2020.05.13.20101253]
[4]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[5]
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]
[6]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[7]
Hodgson, J. The pandemic pipeline. Nat. Biotechnol., 2020, 38(5), 523-532.
[http://dx.doi.org/10.1038/d41587-020-00005-z] [PMID: 32203293]
[8]
Van Norman, G.A. Drugs, devices, and the FDA: Part 1. JACC Basic Transl. Sci., 2016, 1(3), 170-179.
[http://dx.doi.org/10.1016/j.jacbts.2016.03.002] [PMID: 30167510]
[10]
[11]
Mahase, E. Covid-19: US approves remdesivir despite WHO trial showing lack of efficacy. BMJ, 2020, m4120.
[http://dx.doi.org/10.1136/bmj.m4120]
[12]
WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19., https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19
[13]
Turgeon, J.; Michaud, V.; Dow, P.; Rihani, S.R.A.; Deodhar, M.; Arwood, M.; Cicali, B. Risk of drug-induced Long QT syndrome associated with the use of repurposed COVID-19 drugs: A systematic review; MedRxiv, 2020.
[14]
Glenmark announces top-line results from Phase 3 clinical trial of favipiravir for COVID-19 treatment. Express Pharma,, 2020.https://www.expresspharma.in/covid19-updates/glenmark-announces-top-line-results-from-phase-3-clinical-trial-of-favipiravir-for-covid-19-treatment/
[15]
Hung, I.F-N.; Lung, K-C.; Tso, E.Y-K.; Liu, R.; Chung, T.W-H.; Chu, M-Y.; Ng, Y-Y.; Lo, J.; Chan, J.; Tam, A.R.; Shum, H-P.; Chan, V.; Wu, A.K-L.; Sin, K-M.; Leung, W-S.; Law, W-L.; Lung, D.C.; Sin, S.; Yeung, P.; Yip, C.C-Y.; Zhang, R.R.; Fung, A.Y-F.; Yan, E.Y-W.; Leung, K-H.; Ip, J.D.; Chu, A.W-H.; Chan, W-M.; Ng, A.C-K.; Lee, R.; Fung, K.; Yeung, A.; Wu, T-C.; Chan, J.W-M.; Yan, W-W.; Chan, W-M.; Chan, J.F-W.; Lie, A.K-W.; Tsang, O.T-Y.; Cheng, V.C-C.; Que, T-L.; Lau, C-S.; Chan, K-H.; To, K.K-W.; Yuen, K-Y. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial. Lancet, 2020, 395(10238), 1695-1704.
[http://dx.doi.org/10.1016/S0140-6736(20)31042-4] [PMID: 32401715]
[16]
Wang, Z.; Yang, B.; Li, Q.; Wen, L.; Zhang, R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am.,, 2020.
[17]
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]
[18]
Goyal, G.; Phukan, A.C.; Hussain, M.; Lal, V.; Modi, M.; Goyal, M.K.; Sehgal, R. Sorting out difficulties in immunological diagnosis of neurocysticercosis: Development and assessment of real time loop mediated isothermal amplification of cysticercal DNA in blood. J. Neurol. Sci., 2019, 408116544
[http://dx.doi.org/10.1016/j.jns.2019.116544] [PMID: 31759221]
[19]
Warren, T.K.; Jordan, R.; Lo, M.K.; Ray, A.S.; Mackman, R.L.; Soloveva, V.; Siegel, D.; Perron, M.; Bannister, R.; Hui, H.C.; Larson, N.; Strickley, R.; Wells, J.; Stuthman, K.S.; Van Tongeren, S.A.; Garza, N.L.; Donnelly, G.; Shurtleff, A.C.; Retterer, C.J.; Gharaibeh, D.; Zamani, R.; Kenny, T.; Eaton, B.P.; Grimes, E.; Welch, L.S.; Gomba, L.; Wilhelmsen, C.L.; Nichols, D.K.; Nuss, J.E.; Nagle, E.R.; Kugelman, J.R.; Palacios, G.; Doerffler, E.; Neville, S.; Carra, E.; Clarke, M.O.; Zhang, L.; Lew, W.; Ross, B.; Wang, Q.; Chun, K.; Wolfe, L.; Babusis, D.; Park, Y.; Stray, K.M.; Trancheva, I.; Feng, J.Y.; Barauskas, O.; Xu, Y.; Wong, P.; Braun, M.R.; Flint, M.; McMullan, L.K.; Chen, S.S.; Fearns, R.; Swaminathan, S.; Mayers, D.L.; Spiropoulou, C.F.; Lee, W.A.; Nichol, S.T.; Cihlar, T.; Bavari, S. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 2016, 531(7594), 381-385.
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[20]
Siegel, D.; Hui, H.C.; Doerffler, E.; Clarke, M.O.; Chun, K.; Zhang, L.; Neville, S.; Carra, E.; Lew, W.; Ross, B.; Wang, Q.; Wolfe, L.; Jordan, R.; Soloveva, V.; Knox, J.; Perry, J.; Perron, M.; Stray, K.M.; Barauskas, O.; Feng, J.Y.; Xu, Y.; Lee, G.; Rheingold, A.L.; Ray, A.S.; Bannister, R.; Strickley, R.; Swaminathan, S.; Lee, W.A.; Bavari, S.; Cihlar, T.; Lo, M.K.; Warren, T.K.; Mackman, R.L. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J. Med. Chem., 2017, 60(5), 1648-1661.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01594] [PMID: 28124907]
[21]
Chun, B.K.; Clarke, M.O.N.H.; Doerffler, E.; Hui, H.C.; Jordan, R.; Mackman, R.L.; Parrish, J.P.; Ray, A.S.; Siegel, D. Methods for treating Filoviridae virus infections. US9724360B2,, 2017.https://patents.google.com/patent/US9724360B2/en
[22]
Vieira, T.; Stevens, A.C.; Chtchemelinine, A.; Gao, D.; Badalov, P.; Heumann, L. Development of a large-scale cyanation process using continuous flow chemistry en route to the synthesis of remdesivir. Org. Process Res. Dev., 2020, 24, 2113-2121.
[http://dx.doi.org/10.1021/acs.oprd.0c00172]
[23]
De Savi, C.; Hughes, D.L.; Kvaerno, L. Quest for a COVID-19 cure by repurposing small-molecule drugs: Mechanism of action, clinical development, synthesis at scale, and outlook for supply. Org. Process Res. Dev., 2020, 24, 940-976.
[http://dx.doi.org/10.1021/acs.oprd.0c00233]
[24]
Wang, M.; Zhang, L.; Huo, X.; Zhang, Z.; Yuan, Q.; Li, P.; Chen, J.; Zou, Y.; Wu, Z.; Zhang, W. Catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir. Angew. Chem. Int. Ed., 2020.
[25]
Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; Bannister, R.; Park, Y.; Babusis, D.; Clarke, M.O.; Mackman, R.L.; Spahn, J.E.; Palmiotti, C.A.; Siegel, D.; Ray, A.S.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med., 2017, 9(396)eaal3653
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[26]
Mulangu, S.; Dodd, L.E.; Davey, R.T., Jr; Tshiani Mbaya, O.; Proschan, M.; Mukadi, D.; Lusakibanza Manzo, M.; Nzolo, D.; Tshomba Oloma, A.; Ibanda, A.; Ali, R.; Coulibaly, S.; Levine, A.C.; Grais, R.; Diaz, J.; Lane, H.C.; Muyembe-Tamfum, J.J.; Sivahera, B.; Camara, M.; Kojan, R.; Walker, R.; Dighero-Kemp, B.; Cao, H.; Mukumbayi, P.; Mbala-Kingebeni, P.; Ahuka, S.; Albert, S.; Bonnett, T.; Crozier, I.; Duvenhage, M.; Proffitt, C.; Teitelbaum, M.; Moench, T.; Aboulhab, J.; Barrett, K.; Cahill, K.; Cone, K.; Eckes, R.; Hensley, L.; Herpin, B.; Higgs, E.; Ledgerwood, J.; Pierson, J.; Smolskis, M.; Sow, Y.; Tierney, J.; Sivapalasingam, S.; Holman, W.; Gettinger, N.; Vallée, D.; Nordwall, J. PALM Writing Group; PALM Consortium study team. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med., 2019, 381(24), 2293-2303.
[http://dx.doi.org/10.1056/NEJMoa1910993] [PMID: 31774950]
[27]
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]
[28]
Tchesnokov, E.P.; Obikhod, A.; Schinazi, R.F.; Götte, M. Delayed chain termination protects the anti-hepatitis B virus drug entecavir from excision by HIV-1 reverse transcriptase. J. Biol. Chem., 2008, 283(49), 34218-34228.
[http://dx.doi.org/10.1074/jbc.M806797200] [PMID: 18940786]
[29]
Dulin, D.; Arnold, J.J.; van Laar, T.; Oh, H-S.; Lee, C.; Perkins, A.L.; Harki, D.A.; Depken, M.; Cameron, C.E.; Dekker, N.H. Signatures of nucleotide analog incorporation by an RNA-dependent RNA polymerase revealed using high-throughput magnetic tweezers. Cell Rep., 2017, 21(4), 1063-1076.
[http://dx.doi.org/10.1016/j.celrep.2017.10.005] [PMID: 29069588]
[30]
Gordon, C.J.; Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Gotte, 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.
[31]
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.
[32]
Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; Lopez de Castilla, D.; Finberg, R.W.; Dierberg, K.; Tapson, V.; Hsieh, L.; Patterson, T.F.; Paredes, R.; Sweeney, D.A.; Short, W.R.; Touloumi, G.; Lye, D.C.; Ohmagari, N.; Oh, M.; Ruiz-Palacios, G.M.; Benfield, T.; Fätkenheuer, G.; Kortepeter, M.G.; Atmar, R.L.; Creech, C.B.; Lundgren, J.; Babiker, A.G.; Pett, S.; Neaton, J.D.; Burgess, T.H.; Bonnett, T.; Green, M.; Makowski, M.; Osinusi, A.; Nayak, S.; Lane, H.C. Remdesivir for the treatment of COVID-19 — Final report. N. Engl. J. Med., 2020.
[33]
WHO Solidarity trial consortium. H. Pan, R. Peto, Q.A. Karim, M. Alejandria, A.M. Henao-Restrepo, C.H. García, M.-P. Kieny, R. Malekzadeh, S. Murthy, M.-P. Preziosi, S. Reddy, M.R. Periago, V. Sathiyamoorthy, J.-A. Røttingen, S. Swaminathan, as the members of the Writing Committee, assume responsibility for the content and integrity of this article, repurposed antiviral drugs for COVID-19 –interim WHO SOLIDARITY trial results, Infectious Diseases (except. HIV AIDS (Auckl.), 2020.
[http://dx.doi.org/10.1101/2020.10.15.20209817]
[34]
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]
[35]
Liu, J.; Cao, R.; Xu, M.; Wang, X.; Zhang, H.; Hu, H.; Li, Y.; Hu, Z.; Zhong, W.; Wang, M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov., 2020, 6, 16.
[http://dx.doi.org/10.1038/s41421-020-0156-0] [PMID: 32194981]
[36]
Sahraei, Z.; Shabani, M.; Shokouhi, S.; Saffaei, A. Aminoquinolines against coronavirus disease 2019 (COVID-19): Chloroquine or hydroxychloroquine. Int. J. Antimicrob. Agents, 2020, 55(4)105945
[37]
Chen, Z.; Hu, J.; Zhang, Z.; Jiang, S.; Han, S.; Yan, D.; Zhuang, R.; Hu, B.; Zhang, Z. Efficacy of hydroxychloroquine in patients with COVID-19: Results of a randomized clinical trial; MedRxiv, 2020.
[38]
Savarino, A.; Di Trani, L.; Donatelli, I.; Cauda, R.; Cassone, A. New insights into the antiviral effects of chloroquine. Lancet Infect. Dis., 2006, 6(2), 67-69.
[http://dx.doi.org/10.1016/S1473-3099(06)70361-9] [PMID: 16439323]
[39]
Vardanyan, R.S.; Hruby, V.J. Drugs for treating protozoan infections. Synth. Essent. Drugs; Elsevier, 2006, pp. 559-582.
[http://dx.doi.org/10.1016/B978-044452166-8/50037-6]
[40]
Price, C.C.; Roberts, R.M. The synthesis of 4-hydroxyquinolines; through ethoxymethylene malonic ester. J. Am. Chem. Soc., 1946, 68, 1204-1208.
[http://dx.doi.org/10.1021/ja01211a020] [PMID: 20990951]
[41]
Surrey, A.R.; Hammer, H.F. Some 7-substituted 4-aminoquinoline derivatives. J. Am. Chem. Soc., 1946, 68, 113-116.
[http://dx.doi.org/10.1021/ja01205a036] [PMID: 21008327]
[42]
Johnson, W.S.; Buell, B.G. A new synthesis of chloroquine. J. Am. Chem. Soc., 1952, 74, 4513-4516.
[http://dx.doi.org/10.1021/ja01138a014]
[43]
Elderfield, R.C.; Gensler, W.J.; Brody, F.; Head, J.D.; Dickerman, S.C.; Wiederhold, L.; Kremer, C.B.; Hageman, H.A.; Kreysa, F.J.; Griffing, J.M.; Kupchan, S.M.; Newman, B.; Maynard, J.T. Synthesis of l-alkylamino-4-bromopentane derivatives and of other amino halides. J. Am. Chem. Soc., 1946, 68, 1579-1584.
[http://dx.doi.org/10.1021/ja01212a061] [PMID: 20994986]
[44]
Surrey, A.R.; Hammer, H.F. The preparation of 7-Chloro-4-(4-(N-ethyl-N-β-hydroxyethylamino)-1- methylbutylamino)-quinoline and related compounds. J. Am. Chem. Soc., 1950, 72, 1814-1815.
[http://dx.doi.org/10.1021/ja01160a116]
[45]
Mackenzie, J.M.; Westaway, E.G. Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J. Virol., 2001, 75(22), 10787-10799.
[http://dx.doi.org/10.1128/JVI.75.22.10787-10799.2001] [PMID: 11602720]
[46]
Savarino, A.; Gennero, L.; Chen, H.C.; Serrano, D.; Malavasi, F.; Boelaert, J.R.; Sperber, K. .Anti-HIV effects of chloroquine: Mechanisms of inhibition and spectrum of activity. AIDS, 2001, 15(17), 2221-2229., https://journals.lww.com/aidsonline/Fulltext/2001/11230/Anti_HIV_effects_of_chloroquine__mechanisms_of.2.aspx
[http://dx.doi.org/10.1097/00002030-200111230-00002] [PMID: 11698694]
[47]
Savarino, A.; Boelaert, J.R.; Cassone, A.; Majori, G.; Cauda, R. Effects of chloroquine on viral infections: An old drug against today’s diseases? Lancet Infect. Dis., 2003, 3(11), 722-727.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[48]
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]
[49]
Jeong, J.Y.; Jue, D.M. Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages. J. Immunol.,, 1997, 158(10), 4901-4907.
[PMID: 9144507]
[50]
Bondeson, J.; Sundler, R. Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages: Implications for their mode of action in rheumatoid arthritis. Gen. Pharmacol., 1998, 30(3), 357-366.
[http://dx.doi.org/10.1016/S0306-3623(97)00269-3] [PMID: 9510087]
[51]
van den Borne, B.E.; Dijkmans, B.A.; de Rooij, H.H.; le Cessie, S.; Verweij, C.L. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J. Rheumatol., 1997, 24(1), 55-60..
[PMID: 9002011]
[52]
Karres, I.; Kremer, J.P.; Dietl, I.; Steckholzer, U.; Jochum, M.; Ertel, W. Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am. J. Physiol., 1998, 274(4), R1058-R1064.
[http://dx.doi.org/10.1152/ajpregu.1998.274.4.R1058] [PMID: 9575969]
[53]
Picot, S.; Peyron, F.; Donadille, A.; Vuillez, J.P.; Barbe, G.; Ambroise-Thomas, P. Chloroquine-induced inhibition of the production of TNF, but not of IL-6, is affected by disruption of iron metabolism. Immunology, 1993, 80(1), 127-133..
[PMID: 8244453]
[54]
Weber, S.M.; Levitz, S.M. Chloroquine interferes with lipopolysaccharide-induced TNF-alpha gene expression by a nonlysosomotropic mechanism. J. Immunol., 2000, 165(3), 1534-1540.
[http://dx.doi.org/10.4049/jimmunol.165.3.1534] [PMID: 10903761]
[55]
Jeong, J-Y.; Choi, J.W.; Jeon, K-I.; Jue, D-M. Chloroquine decreases cell-surface expression of tumour necrosis factor receptors in human histiocytic U-937 cells. Immunology, 2002, 105(1), 83-91.
[http://dx.doi.org/10.1046/j.0019-2805.2001.01339.x] [PMID: 11849318]
[56]
Wang, L-F.; Lin, Y-S.; Huang, N-C.; Yu, C-Y.; Tsai, W-L.; Chen, J-J.; Kubota, T.; Matsuoka, M.; Chen, S-R.; Yang, C-S.; Lu, R-W.; Lin, Y-L.; Chang, T-H. Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J. Interferon Cytokine Res., 2015, 35(3), 143-156.
[http://dx.doi.org/10.1089/jir.2014.0038] [PMID: 25321315]
[57]
Singh, A.K.; Singh, A.; Shaikh, A.; Singh, R.; Misra, A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab. Syndr., 2020, 14(3), 241-246.
[http://dx.doi.org/10.1016/j.dsx.2020.03.011] [PMID: 32247211]
[58]
Mauthe, M.; Orhon, I.; Rocchi, C.; Zhou, X.; Luhr, M.; Hijlkema, K-J.; Coppes, R.P.; Engedal, N.; Mari, M.; Reggiori, F. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy, 2018, 14(8), 1435-1455.
[http://dx.doi.org/10.1080/15548627.2018.1474314] [PMID: 29940786]
[59]
Devaux, C.A.; Rolain, J-M.; Colson, P.; Raoult, D. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int. J. Antimicrob. Agents, 2020, 55(5)105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[60]
Lv, P.; Zhu, L.; Yu, Y.; Wang, W.; Liu, G.; Lu, H. Effect of NaOH concentration on antibacterial activities of Cu nanoparticles and the antibacterial mechanism. Mater. Sci. Eng. C, 2020, 110110669
[http://dx.doi.org/10.1016/j.msec.2020.110669] [PMID: 32204097]
[61]
Chowdhury, M.S.; Rathod, J.; Gernsheimer, J. A rapid systematic review of clinical trials utilizing chloroquine and hydroxychloroquine as a treatment for COVID-19. Acad. Emerg. Med., 2020, 27(6), 493-504.
[62]
Abella, B.S. Jolkovsky, E.L.; Biney, B.T.; Uspal, J.E.; Hyman, M.C.; Frank, I.; Hensley, S.E.; Gill, S.; Vogl, D.T.; Maillard, I.; Babushok, D.V.; Huang, A.C.; Nasta, S.D.; Walsh, J.C.; Wiletyo, E.P.; Gimotty, P.A.; Milone, M.C.; Amaravadi, R.K. and the prevention and treatment of COVID-19 with hydroxychloroquine (PATCH) investigators. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: A randomized clinical trial. JAMA Intern. Med., 2020, 181(2), 195-202.
[http://dx.doi.org/10.1001/jamainternmed.2020.6319] [PMID: 33001138]
[63]
Furuta, Y.; Takahashi, K.; Fukuda, Y.; Kuno, M.; Kamiyama, T.; Kozaki, K.; Nomura, N.; Egawa, H.; Minami, S.; Watanabe, Y.; Narita, H.; Shiraki, K. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob. Agents Chemother., 2002, 46(4), 977-981.
[http://dx.doi.org/10.1128/AAC.46.4.977-981.2002] [PMID: 11897578]
[64]
Furuta, Y.; Takahashi, K.; Kuno-Maekawa, M.; Sangawa, H.; Uehara, S.; Kozaki, K.; Nomura, N.; Egawa, H.; Shiraki, K. Mechanism of action of T-705 against influenza virus. Antimicrob. Agents Chemother., 2005, 49(3), 981-986.
[http://dx.doi.org/10.1128/AAC.49.3.981-986.2005] [PMID: 15728892]
[65]
Furuta, Y.; Takahashi, K.; Shiraki, K.; Sakamoto, K.; Smee, D.F.; Barnard, D.L.; Gowen, B.B.; Julander, J.G.; Morrey, J.D. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res., 2009, 82(3), 95-102.
[http://dx.doi.org/10.1016/j.antiviral.2009.02.198] [PMID: 19428599]
[66]
Egawa, H.; Furuta, Y. Nitrogenous heterocyclic carboxamide derivatives or salts thereof and antiviral agents containing both. EP1112743A1, . 2001.https://patents.google.com/patent/EP1112743A1/ja
[67]
Liu, F.L.; Li, C.Q.; Xiang, H.Y.; Feng, S. A practical and step-economic route to Favipiravir. Chem. Pap., 2017, 71, 2153-2158.
[http://dx.doi.org/10.1007/s11696-017-0208-6]
[68]
Jordis, U.; Beldar, S. Synthetic studies towards the antiviral pyrazine derivative T-705. Proc. 13th Int. Electron. Conf. Synth. Org. Chem., MDPI, Sciforum.net, 2009, p. 223..
[http://dx.doi.org/10.3390/ecsoc-13-00223]
[69]
Tamio, H.; Naoki, N.; Hiraoki, K.; Takuya, K. Method for producing dichloropyrazine derivative. WO2010087117A1,, 2010.https://patents.google.com/patent/WO2010087117A1/en
[70]
Guo, Q.; Xu, M.; Guo, S.; Zhu, F.; Xie, Y.; Shen, J. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. Pap., 2019, 73, 1043-1051.
[http://dx.doi.org/10.1007/s11696-018-0654-9]
[71]
Titova, Y.A.; Fedorova, O.V. Favipiravir - a modern antiviral drug: Synthesis and modifications. Chem Heterocycl Compd (N Y), 2020, 56, 1-4.
[http://dx.doi.org/10.1007/s10593-020-02715-3] [PMID: 32836314]
[72]
Dong, L.; Hu, S.; Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58-60.
[http://dx.doi.org/10.5582/ddt.2020.01012] [PMID: 32147628]
[73]
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]
[74]
Rocha-Pereira, J.; Jochmans, D.; Dallmeier, K.; Leyssen, P.; Nascimento, M.S.J.; Neyts, J. Favipiravir (T-705) inhibits in vitro norovirus replication. Biochem. Biophys. Res. Commun., 2012, 424(4), 777-780.
[http://dx.doi.org/10.1016/j.bbrc.2012.07.034] [PMID: 22809499]
[75]
Jin, Z.; Smith, L.K.; Rajwanshi, V.K.; Kim, B.; Deval, J. The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5′-triphosphate towards influenza A virus polymerase. PLoS One, 2013, 8(7)e68347
[http://dx.doi.org/10.1371/journal.pone.0068347] [PMID: 23874596]
[76]
Furuta, T.Y.; Komeno, T.; Nakamuba, T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2017, 93, 449-463.
[http://dx.doi.org/10.2183/pjab.93.027]
[77]
Baranovich, T.; Wong, S-S.; Armstrong, J.; Marjuki, H.; Webby, R.J.; Webster, R.G.; Govorkova, E.A. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J. Virol., 2013, 87(7), 3741-3751.
[http://dx.doi.org/10.1128/JVI.02346-12] [PMID: 23325689]
[78]
Tu, Y-F.; Chien, C-S.; Yarmishyn, A.A.; Lin, Y-Y.; Luo, Y-H.; Lin, Y-T.; Lai, W-Y.; Yang, D-M.; Chou, S-J.; Yang, Y-P.; Wang, M-L.; Chiou, S-H. A review of SARS-CoV-2 and the ongoing clinical trials. Int. J. Mol. Sci., 2020, 21(7), 2657.
[http://dx.doi.org/10.3390/ijms21072657] [PMID: 32290293]
[79]
Chen, C.; Zhang, Y.; Huang, J.; Yin, P.; Cheng, Z.; Wu, J.; Chen, S.; Zhang, Y.; Chen, B.; Lu, M.; Luo, Y.; Ju, L.; Zhang, J.; Wang, X. Favipiravir versus arbidol for COVID-19: A randomized clinical trial; MedRxiv, 2020.
[80]
Zhao, H.; Zhu, Q.; Zhang, C.; Li, J.; Wei, M.; Qin, Y.; Chen, G.; Wang, K.; Yu, J.; Wu, Z.; Chen, X.; Wang, G. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed. Pharmacother., 2020.110825
[http://dx.doi.org/10.1016/j.biopha.2020.110825]
[81]
No significant benefit of Umifenovir in COVID-19 treatment: Glenmark, Health News, ET HealthWorld.. https://health.economictimes.indiatimes.com/news/pharma/no-significant-benefit-of-umifenovir-in-covid-19-treatment-glenmark/78581691
[82]
Chandwani, A.; Shuter, J. Lopinavir/ritonavir in the treatment of HIV-1 infection: A review. Ther. Clin. Risk Manag., 2008, 4(5), 1023-1033.
[http://dx.doi.org/10.2147/TCRM.S3285] [PMID: 19209283]
[83]
Fischer, J.; Ganellin, C.R. Analogue-based drug discovery; Wiley-VCH: Weinheim, 2006. http://public.ebookcentral.proquest.com/choice/publicfullrecord.aspx?p=481323
[http://dx.doi.org/10.1002/3527608001]
[84]
Sham, H.L.; Norbeck, D.W.; Chen, X.; Betebenner, D.A. Betebenner, Retroviral protease inhibiting compounds. US5914332A, , 1999.https://patents.google.com/patent/US5914332A/en?oq=5914332
[85]
Kempf, D.J.; Marsh, K.C.; Denissen, J.F.; McDonald, E.; Vasavanonda, S.; Flentge, C.A.; Green, B.E.; Fino, L.; Park, C.H.; Kong, X.P. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc. Natl. Acad. Sci. USA, 1995, 92(7), 2484-2488.
[http://dx.doi.org/10.1073/pnas.92.7.2484] [PMID: 7708670]
[86]
Kempf, D.J.; Norbeck, D.W.; Sham, H.L.; Zhao, C.; Sowin, T.J.; Reno, D.S.; Haight, A.R.; Cooper, A.J. Retroviral protease inhibiting compounds. WO1994014436A1, 1994.https://patents.google.com/patent/WO1994014436A1/en?oq=WO+9414436
[87]
Kempf, D.J.; Sham, H.L.; Marsh, K.C.; Flentge, C.A.; Betebenner, D.; Green, B.E.; McDonald, E.; Vasavanonda, S.; Saldivar, A.; Wideburg, N.E.; Kati, W.M.; Ruiz, L.; Zhao, C.; Fino, L.; Patterson, J.; Molla, A.; Plattner, J.J.; Norbeck, D.W. Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy. J. Med. Chem., 1998, 41(4), 602-617.
[http://dx.doi.org/10.1021/jm970636+] [PMID: 9484509]
[88]
Robbins, B.L.; Capparelli, E.V.; Chadwick, E.G.; Yogev, R.; Serchuck, L.; Worrell, C.; Smith, M.E.; Alvero, C.; Fenton, T.; Heckman, B.; Pelton, S.I.; Aldrovandi, G.; Borkowsky, W.; Rodman, J.; Havens, P.L. PACTG 1038 Team. Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors. Antimicrob. Agents Chemother., 2008, 52(9), 3276-3283.
[http://dx.doi.org/10.1128/AAC.00224-08] [PMID: 18625762]
[89]
Vardanyan, R.S.; Hruby, V.J. Synthesis of best-seller drugs; Elsevier: Amsterdam, AP, 2016.
[90]
Haight, A.R.; Stuk, T.L.; Menzia, J.A.; Robbins, T.A. A convenient synthesis of enaminones using tandem acetonitrile condensation, Grignard addition. Tetrahedron Lett., 1997, 38, 4191-4194.
[http://dx.doi.org/10.1016/S0040-4039(97)00866-6]
[91]
Stuk, T.L.; Haight, A.R.; Scarpetti, D.; Allen, M.S.; Menzia, J.A.; Robbins, T.A.; Parekh, S.I.; Langridge, D.C.; Tien, J-H.J. An efficient stereocontrolled strategy for the synthesis of hydroxyethylene dipeptide isosteres. J. Org. Chem., 1994, 59, 4040-4041.
[http://dx.doi.org/10.1021/jo00094a006]
[92]
Ghosh, A.K.; Bilcer, G.; Schiltz, G. Syntheses of FDA approved HIV protease inhibitors. Synthesis (Stuttg), 2001, 2001(15), 2203-2229.
[http://dx.doi.org/10.1055/s-2001-18434] [PMID: 30393404]
[93]
Baker, W.R.; Pratt, J.K. Dipeptide isosteres. 2. Synthesis of hydroxyethylene dipeptide isostere diastereomers from a common γ-lactone intermediate. Preparation of renin and HIV-1 protease inhibitor transition state mimics. Tetrahedron, 1993, 49, 8739-8756.
[http://dx.doi.org/10.1016/S0040-4020(01)81896-2]
[94]
Ghosh, A.K.; Shin, D.; Mathivanan, P. Asymmetric dihydroxylation route to a dipeptide isostere of a protease inhibitor: Enantioselective synthesis of the core unit of ritonavir. Chem. Commun. (Camb.), 1999, 1999(11), 1025-1026.
[http://dx.doi.org/10.1039/a902518i] [PMID: 30364548]
[95]
Kempf, D.J.; Marsh, K.C.; Fino, L.C.; Bryant, P.; Craig-Kennard, A.; Sham, H.L.; Zhao, C.; Vasavanonda, S.; Kohlbrenner, W.E.; Wideburg, N.E.; Saldivar, A.; Green, B.E.; Herrin, T.; Norbeck, D.W. Design of orally bioavailable, symmetry-based inhibitors of HIV protease. Bioorg. Med. Chem., 1994, 2(9), 847-858.
[http://dx.doi.org/10.1016/S0968-0896(00)82036-2] [PMID: 7712122]
[96]
Stoner, E.J.; Cooper, A.J.; Dickman, D.A.; Kolaczkowski, L.; Lallaman, J.E.; Liu, J-H.; Oliver-Shaffer, P.A.; Patel, K.M.; Paterson, J.B.; Plata, D.J.; Riley, D.A. Hing.L. Sham, P.J. Stengel, J.-H.J. Tien. Synthesis of HIV protease inhibitor ABT-378 (Lopinavir). Org. Process Res. Dev., 2000, 4, 264-269.
[http://dx.doi.org/10.1021/op990202j]
[97]
Stoner, E.J.; Stengel, P.J.; Cooper, A.J. Synthesis of ABT-378, an HIV protease inhibitor candidate: Avoiding the use of carbodiimides in a difficult peptide coupling. Org. Process Res. Dev., 1999, 3, 145-148.
[http://dx.doi.org/10.1021/op980214p]
[98]
Huang, X.; Xu, Y.; Yang, Q.; Chen, J.; Zhang, T.; Li, Z.; Guo, C.; Chen, H.; Wu, H.; Li, N. Efficacy and biological safety of lopinavir/ritonavir based anti-retroviral therapy in HIV-1-infected patients: A meta-analysis of randomized controlled trials. Sci. Rep., 2015, 5, 8528.
[http://dx.doi.org/10.1038/srep08528] [PMID: 25704206]
[99]
Snijder, E.J.; Bredenbeek, P.J.; Dobbe, J.C.; Thiel, V.; Ziebuhr, J.; Poon, L.L.M.; Guan, Y.; Rozanov, M.; Spaan, W.J.M.; Gorbalenya, A.E. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J. Mol. Biol., 2003, 331(5), 991-1004.
[http://dx.doi.org/10.1016/S0022-2836(03)00865-9] [PMID: 12927536]
[100]
Zhang, X.W.; Yap, Y.L. Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs. Bioorg. Med. Chem., 2004, 12(10), 2517-2521.
[http://dx.doi.org/10.1016/j.bmc.2004.03.035] [PMID: 15110833]
[101]
Chen, F.; Chan, K.H.; Jiang, Y.; Kao, R.Y.T.; Lu, H.T.; Fan, K.W.; Cheng, V.C.C.; Tsui, W.H.W.; Hung, I.F.N.; Lee, T.S.W.; Guan, Y.; Peiris, J.S.M.; Yuen, K.Y. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J. Clin. Virol., 2004, 31(1), 69-75.
[http://dx.doi.org/10.1016/j.jcv.2004.03.003] [PMID: 15288617]
[102]
Chu, C.M.; Cheng, V.C.C.; Hung, I.F.N.; Wong, M.M.L.; Chan, K.H.; Chan, K.S.; Kao, R.Y.T.; Poon, L.L.M.; Wong, C.L.P.; Guan, Y.; Peiris, J.S.M.; Yuen, K.Y. HKU/UCH SARS Study Group Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax, 2004, 59(3), 252-256.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[103]
Yamamoto, N.; Yang, R.; Yoshinaka, Y.; Amari, S.; Nakano, T.; Cinatl, J.; Rabenau, H.; Doerr, H.W.; Hunsmann, G.; Otaka, A.; Tamamura, H.; Fujii, N.; Yamamoto, N. HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus. Biochem. Biophys. Res. Commun., 2004, 318(3), 719-725.
[http://dx.doi.org/10.1016/j.bbrc.2004.04.083] [PMID: 15144898]
[104]
de Wilde, A.H.; Jochmans, D.; Posthuma, C.C.; Zevenhoven-Dobbe, J.C.; van Nieuwkoop, S.; Bestebroer, T.M.; van den Hoogen, B.G.; Neyts, J.; Snijder, E.J. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother., 2014, 58(8), 4875-4884.
[http://dx.doi.org/10.1128/AAC.03011-14] [PMID: 24841269]
[105]
Chan, J.F-W.; Yao, Y.; Yeung, M-L.; Deng, W.; Bao, L.; Jia, L.; Li, F.; Xiao, C.; Gao, H.; Yu, P.; Cai, J-P.; Chu, H.; Zhou, J.; Chen, H.; Qin, C.; Yuen, K-Y. Treatment With Lopinavir/Ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J. Infect. Dis., 2015, 212(12), 1904-1913.
[http://dx.doi.org/10.1093/infdis/jiv392] [PMID: 26198719]
[106]
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]
[107]
Baden, L.R.; Rubin, E.J. Covid-19 - The search for effective therapy. N. Engl. J. Med., 2020, 382(19), 1851-1852.
[http://dx.doi.org/10.1056/NEJMe2005477] [PMID: 32187463]
[108]
Horby, P.W.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Emberson, J.; Palfreeman, A.; Raw, J.; Elmahi, E.; Prudon, B.; Green, C.; Carley, S.; Chadwick, D.; Davies, M.; Wise, M.P.; Baillie, J.K.; Chappell, L.C.; Faust, S.N.; Jaki, T.; Jefferey, K.; Lim, W.S.; Montgomery, A.; Rowan, K.; Juszczak, E.; Haynes, R.; Landray, M.J. . RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet, 2020, 396, 1345-1352.
[http://dx.doi.org/10.1016/S0140-6736(20)32013-4] [PMID: 33031764]
[109]
Khalili, J.S.; Zhu, H.; Mak, N.S.A.; Yan, Y.; Zhu, Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J. Med. Virol., 2020, 92(7), 740-746.
[110]
Witkowski, J.T.; Robins, R.K.; Sidwell, R.W.; Simon, L.N. Design, synthesis, and broad spectrum antiviral activity of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. J. Med. Chem., 1972, 15(11), 1150-1154.
[http://dx.doi.org/10.1021/jm00281a014] [PMID: 4347550]
[111]
Derudas, M.; Brancale, A.; Naesens, L.; Neyts, J.; Balzarini, J.; McGuigan, C. Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin. Bioorg. Med. Chem., 2010, 18(7), 2748-2755.
[http://dx.doi.org/10.1016/j.bmc.2010.02.015] [PMID: 20207546]
[112]
Li, Y.S.; Zhang, J.J.; Mei, L.Q.; Tan, C.X. An improved procedure for the preparation of ribavirin. Org. Prep. Proced. Int., 2012, 44, 387-391.
[http://dx.doi.org/10.1080/00304948.2012.697741]
[113]
Sakharov, V.; Baykov, S.; Konstantinova, I.; Esipov, R.; Dorogov, M. An efficient chemoenzymatic process for preparation of ribavirin. Int. J. Chem. Eng., 2015, 1-5.
[114]
Barai, V.N.; Zinchenko, A.I.; Eroshevskaya, L.A.; Kalinichenko, E.N.; Kulak, T.I.; Mikhailopulo, I.A. A universal biocatalyst for the preparation of base- and sugar-modified nucleosides via an enzymatic transglycosylation. Helv. Chim. Acta, 2002, 85, 1901-1908.
[http://dx.doi.org/10.1002/1522-2675(200207)85:7<1901:AID-HLCA1901>3.0.CO;2-C]
[115]
Nóbile, M.; Terreni, M.; Lewkowicz, E.; Iribarren, A.M. Aeromonas hydrophila strains as biocatalysts for transglycosylation. Biocatal. Biotransform., 2010, 28, 395-402.
[http://dx.doi.org/10.3109/10242422.2010.538949]
[116]
Chen, N.; Xing, C-G.; Xie, X-X.; Xu, Q-Y. Optimization of technical conditions of producing ribavirin by Bacillus subtilis. Ann. Microbiol., 2009, 59, 525-530.
[http://dx.doi.org/10.1007/BF03175141]
[117]
De Clercq, E.; Li, G. Approved antiviral drugs over the past 50 years. Clin. Microbiol. Rev., 2016, 29(3), 695-747.
[http://dx.doi.org/10.1128/CMR.00102-15] [PMID: 27281742]
[118]
Graci, J.D.; Cameron, C.E. Mechanisms of action of ribavirin against distinct viruses. Rev. Med. Virol., 2006, 16(1), 37-48.
[http://dx.doi.org/10.1002/rmv.483] [PMID: 16287208]
[119]
Crotty, S.; Cameron, C.E.; Andino, R. RNA virus error catastrophe: Direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA, 2001, 98(12), 6895-6900.
[http://dx.doi.org/10.1073/pnas.111085598] [PMID: 11371613]
[120]
Kobayashi, T.; Nakatsuka, K.; Shimizu, M.; Tamura, H.; Shinya, E.; Atsukawa, M.; Harimoto, H.; Takahashi, H.; Sakamoto, C. Ribavirin modulates the conversion of human CD4(+) CD25(-) T cell to CD4(+) CD25(+) FOXP3(+) T cell via suppressing interleukin-10-producing regulatory T cell. Immunology, 2012, 137(3), 259-270.
[http://dx.doi.org/10.1111/imm.12005] [PMID: 22891772]
[121]
Tam, R.C.; Pai, B.; Bard, J.; Lim, C.; Averett, D.R.; Phan, U.T.; Milovanovic, T. Ribavirin polarizes human T cell responses towards a type 1 cytokine profile. J. Hepatol., 1999, 30(3), 376-382.
[http://dx.doi.org/10.1016/S0168-8278(99)80093-2] [PMID: 10190717]
[122]
Zhang, Y.; Xu, Q.; Sun, Z.; Zhou, L. Current targeted therapeutics against COVID-19: Based on first-line experience in China. Pharmacol. Res., 2020, 157104854
[http://dx.doi.org/10.1016/j.phrs.2020.104854] [PMID: 32360585]
[123]
Wright, Z.V.F.; Wu, N.C.; Kadam, R.U.; Wilson, I.A.; Wolan, D.W. Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin. Bioorg. Med. Chem. Lett., 2017, 27(16), 3744-3748.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.074] [PMID: 28689973]
[124]
Wilson, I.A. WOLAN, D.W.; WRIGHT, Z.V.F.; KADAM, R.U.; WU, N.C. Arbidol analogs with improved influenza hemagglutinin potency. WO2018112128A1,, 2018.https://patents.google.com/patent/WO2018112128A1/en
[125]
Trofimov, F.A.; Tsyshkova, N.G.; Zotova, S.A.; Grinev, A.N. Synthesis of a new antiviral agent, arbidole. Pharm. Chem. J., 1993, 27, 75-76.
[http://dx.doi.org/10.1007/BF00772858]
[126]
Cao, Z.; Dong, J.; Shi, L. Preparation method of arbidol hydrochloride. CN102351778A,, 2012.https://patents.google.com/patent/CN102351778A/en
[127]
Chai, H.; Zhao, Y.; Zhao, C.; Gong, P. Synthesis and in vitro anti-hepatitis B virus activities of some ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates. Bioorg. Med. Chem., 2006, 14(4), 911-917.
[http://dx.doi.org/10.1016/j.bmc.2005.08.041] [PMID: 16183290]
[128]
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]
[129]
Huang, L.; Zhang, L.; Liu, Y.; Luo, R.; Zeng, L.; Telegina, I.; Vlassov, V.V. Arbidol for preventing and treating influenza in adults and children. Cochrane Database Syst. Rev., 2017, 2.
[http://dx.doi.org/10.1002/14651858.CD011489]
[130]
Lopinavir/ritonavir and Arbidol not effective for mild-to-moderate COVID-19. Eur. Pharm. Rev,, https://www.europeanpharmaceuticalreview.com/news/117273/trial-finds-lopinavir-ritonavir-and-arbidol-ineffective-for-mild-to-moderate-covid-19/
[131]
Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. medRxiv,, https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v4
[132]
Rapolu, R.K.; Areveli, S.; Raju, V.V.N.K.V.P.; Navuluri, S.; Chavali, M.; Mulakayala, N. An efficient synthesis of darunavir substantially free from impurities: Synthesis and characterization of novel impurities. ChemistrySelect, 2019, 4, 4422-4427.
[http://dx.doi.org/10.1002/slct.201803825]
[133]
Babu, K.R.; Rao, V.K.; Sudhakar, Y.; Raju, C.N. First stereoselective total synthesis of (3R, 3aS, 6aR)-hexahydrofuro[2,3-b]furan- 3-yl (2R,3S)-4-(4-amino-N-isobutyl phenylsulfonamido)-3-hydroxy-1- phenylbutan-2-yl-carbamate (diastereomer of Darunavir). Indian J. Chem., 2012, 6.
[134]
Lack of evidence to support use of darunavir-based treatments for SARS-CoV-2. Johnson & Johnson, Content Lab US,, https://www.jnj.com/lack-of-evidence-to-support-darunavir-based-hiv-treatments-for-coronavirus
[135]
Dierynck, I.; Van Marck, H.; Van Ginderen, M.; Jonckers, T.H.M.; Nalam, M.N.L.; Schiffer, C.A.; Raoof, A.; Kraus, G.; Picchio, G. TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows in vitro an improved resistance profile and higher genetic barrier to resistance compared with current protease inhibitors. Antimicrob. Agents Chemother., 2011, 55(12), 5723-5731.
[http://dx.doi.org/10.1128/AAC.00748-11] [PMID: 21896904]
[136]
Chinese Clinical Trial Register (ChiCTR) - The world health organization international clinical trials registered organization registered platform., http://www.chictr.org.cn/showprojen.aspx?proj=49075
[137]
Zhang, Q.; Ma, B-W.; Wang, Q-Q.; Wang, X-X.; Hu, X.; Xie, M-S.; Qu, G-R.; Guo, H-M. The synthesis of tenofovir and its analogues via asymmetric transfer hydrogenation. Org. Lett., 2014, 16(7), 2014-2017.
[http://dx.doi.org/10.1021/ol500583d] [PMID: 24650095]
[138]
Study comparing lopinavir/ritonavir (LPV/r) + emtricitabine/ tenofovir disoproxil fumarate (FTC/TDF) with a nucleoside sparing regimen consisting of lopinavir/ritonavir + raltegravir (RAL)., https://clinicaltrials.gov/ct2/show/NCT00711009
[139]
Toots, M.; Yoon, J-J.; Cox, R.M.; Hart, M.; Sticher, Z.M.; Makhsous, N.; Plesker, R.; Barrena, A.H.; Reddy, P.G.; Mitchell, D.G.; Shean, R.C.; Bluemling, G.R.; Kolykhalov, A.A.; Greninger, A.L.; Natchus, M.G.; Painter, G.R.; Plemper, R.K. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci. Transl. Med., 2019, 11(515)
[http://dx.doi.org/10.1126/scitranslmed.aax5866] [PMID: 31645453]
[140]
Ridgeback biotherapeutics and drug innovations ventures at Emory partner to develop clinical stage coronavirus treatment., https://www.prnewswire.com/news-releases/ridgeback-biotherapeutics-and-drug-innovations-ventures-at-emory-partner-to-develop-clinical-stage-coronavirus-treatment-301027190.html
[141]
Wiltshire, H.R.; Prior, K.J.; Dhesi, J.; Trach, F.; Schlageter, M.; Schönenberger, H. The synthesis of labelled forms of saquinavir. J. Labelled Comp. Radiopharm., 1998, 41, 1103-1126.
[http://dx.doi.org/10.1002/(SICI)1099-1344(199812)41:12<1103:AID-JLCR157>3.0.CO;2-M]
[142]
Göbring, W.; Gokbale, S.; Hilpert, H.; Roessler, F.; Schlageter, M.; Vogt, P. Synthesis of the HIV-proteinase inhibitor saquinavir: A challenge for process research. Chim. Int. J. Chem., 1996, 50, 532- 537., https://www.ingentaconnect.com/content/scs/chimia/1996/00000050/00000011/art00007
[144]
Warren, T.K.; Wells, J.; Panchal, R.G.; Stuthman, K.S.; Garza, N.L.; Van Tongeren, S.A.; Dong, L.; Retterer, C.J.; Eaton, B.P.; Pegoraro, G.; Honnold, S.; Bantia, S.; Kotian, P.; Chen, X.; Taubenheim, B.R.; Welch, L.S.; Minning, D.M.; Babu, Y.S.; Sheridan, W.P.; Bavari, S. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature, 2014, 508(7496), 402-405.
[http://dx.doi.org/10.1038/nature13027] [PMID: 24590073]
[145]
BioCryst completes phase 1 clinical trial of Galidesivir | BioCryst Pharmaceuticals., http://ir.biocryst.com/news-releases/news-release-details/biocryst-completes-phase-1-clinical-trial-galidesivir
[146]
Seiwert, S.D.; Kossen, K.; Pan, L.; Liu, J.; Buckman, B.O. Discovery and development of the HCV NS3/4A protease inhibitor Danoprevir (ITMN-191/RG7227). Antivir. Drugs; John Wiley & Sons, Ltd, 2011, pp. 257-271.
[http://dx.doi.org/10.1002/9780470929353.ch18]
[147]
Jiang, Y.; Andrews, S.W.; Condroski, K.R.; Buckman, B.; Serebryany, V.; Wenglowsky, S.; Kennedy, A.L.; Madduru, M.R.; Wang, B.; Lyon, M.; Doherty, G.A.; Woodard, B.T.; Lemieux, C.; Geck Do, M.; Zhang, H.; Ballard, J.; Vigers, G.; Brandhuber, B.J.; Stengel, P.; Josey, J.A.; Beigelman, L.; Blatt, L.; Seiwert, S.D. Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease. J. Med. Chem., 2014, 57(5), 1753-1769.
[http://dx.doi.org/10.1021/jm400164c] [PMID: 23672640]
[148]
Efficacy and safety of Ganovo (Danoprevir) combined with ritonavir in the treatment of SARS-CoV-2 infection., https://clinicaltrials.gov/ct2/show/NCT04345276
[149]
Caso, M.F.; D’Alonzo, D.; D’Errico, S.; Palumbo, G.; Guaragna, A. Highly stereoselective synthesis of lamivudine (3TC) and emtricitabine (FTC) by a novel N-glycosidation procedure. Org. Lett., 2015, 17(11), 2626-2629.
[http://dx.doi.org/10.1021/acs.orglett.5b00982] [PMID: 25965958]
[150]
Mandala, D.; Watts, P. An improved synthesis of lamivudine and emtricitabine. ChemistrySelect, 2017, 2, 1102-1105.
[http://dx.doi.org/10.1002/slct.201700052]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy