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Anti-Infective Agents

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ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

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Review Article

Anti-HIV Integrase Inhibitors as New Candidates for the Treatment of COVID-19: A Narrative Literature Review

Author(s): Sofia Salari, Hedyieh Karbasforooshan and Hesamoddin Hosseinjani*

Volume 20, Issue 2, 2022

Article ID: e280921196843 Pages: 6

DOI: 10.2174/2211352519666210928110627

Price: $65

Abstract

Background: The initial reports of a contagious novel Severe Acute Respiratory Syndrome- Coronavirus-2 (SARS-CoV-2) were proclaimed by Wuhan, Hubei province, China. This pathogen quickly became a health concern due to the World Health Organization's (WHO) alarm of its pandemic essence. Hence, there is an urgent need for efficacious and curative therapy against COVID-19.

Objective: Theoretically, repurposing anti-viral drugs, specifically HIV treatments, could help meet the urgent need for treating COVID-19 due to the structural similarities of their critical enzyme substrates. Integrase inhibitors are a category of anti-HIV drugs that inhibit integrase strand transfer. In this review, we investigate the binding affinity and stability of raltegravir, dolutegravir, bictegravir, and elvitegravir in interactions with crucial enzymes of coronavirus.

Methods: A literature search was conducted using scientific databases such as Web of Science, Medline (PubMed), Scopus, Google Scholar, and Embase from commencement to September 2020. The most relevant articles regarding the potential effects of integrase inhibitors against COVID-19 were gathered. Ultimately, ten original articles related to the searched terms were selected for this narrative review.

Results: Apparently, in addition to the recent drugs prescribed to cure SARS-CoV-2, integrase inhibitors are promising drugs for repurposing in COVID-19 treatment. Several studies on raltegravir, dolutegravir, bictegravir and elvitegravir were conducted using virtual screening to guess either they are effective or not. Encouraging results were mostly reported for raltegravir and dolutegravir. Nevertheless, bictegravir and elvitegravir need more investigations.

Conclusion: Further experimental and clinical studies of antiviral drugs are necessary to introduce appropriate treatment options for COVID-19.

Keywords: Coronavirus, SARS-CoV-2, COVID-19, integrase inhibitors, raltegravir, dolutegravir.

Graphical Abstract

[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. 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]
Hui, D.S.; I Azhar, E.; Madani, T.A.; Ntoumi, F.; Kock, R.; Dar, O.; Ippolito, G.; Mchugh, T.D.; Memish, Z.A.; Drosten, C.; Zumla, A.; Petersen, E. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis., 2020, 91, 264-266.
[http://dx.doi.org/10.1016/j.ijid.2020.01.009] [PMID: 31953166]
[3]
Zhou, Y.; Hou, Y.; Shen, J.; Huang, Y.; Martin, W.; Cheng, F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov., 2020, 6(1), 14.
[http://dx.doi.org/10.1038/s41421-020-0153-3] [PMID: 33723226]
[4]
Woo, P.C.; Huang, Y.; Lau, S.K.; Yuen, K-Y. Coronavirus genomics and bioinformatics analysis. Viruses, 2010, 2(8), 1804-1820.
[http://dx.doi.org/10.3390/v2081803] [PMID: 21994708]
[5]
Hussain, S.; Pan, J.; Chen, Y.; Yang, Y.; Xu, J.; Peng, Y.; Wu, Y.; Li, Z.; Zhu, Y.; Tien, P.; Guo, D. Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J. Virol., 2005, 79(9), 5288-5295.
[http://dx.doi.org/10.1128/JVI.79.9.5288-5295.2005] [PMID: 15827143]
[6]
Wong, S.K.; Li, W.; Moore, M.J.; Choe, H.; Farzan, M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem., 2004, 279(5), 3197-3201.
[http://dx.doi.org/10.1074/jbc.C300520200] [PMID: 14670965]
[7]
Sarma, P.; Shekhar, N.; Prajapat, M. In silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J. Biomol. Struct. Dyn., 2020, 39(8), 2724-2732.
[PMID: 32266867]
[8]
Cui, J.; Li, F.; Shi, Z-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol., 2019, 17(3), 181-192.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[9]
Ahmed, S.; Mahtarin, R.; Ahmed, S.S.; Akter, S.; Islam, M.S.; Mamun, A.A.; Islam, R.; Hossain, M.N.; Ali, M.A.; Sultana, M.U.C.; Parves, M.R.; Ullah, M.O.; Halim, M.A. Investigating the binding affinity, interaction, and structure-activity-relationship of 76 prescription antiviral drugs targeting RdRp and Mpro of SARS-CoV-2. J. Biomol. Struct. Dyn., 2020, 1-16.
[http://dx.doi.org/10.1080/07391102.2020.1796804] [PMID: 32720571]
[10]
Chrebet, G.L.; Wisniewski, D.; Perkins, A.L.; Deng, Q.; Kurtz, M.B.; Marcy, A.; Parent, S.A. Cell-based assays to detect inhibitors of fungal mRNA capping enzymes and characterization of sinefungin as a cap methyltransferase inhibitor. J. Biomol. Screen., 2005, 10(4), 355-364.
[http://dx.doi.org/10.1177/1087057104273333] [PMID: 15964937]
[11]
Zeng, C.; Wu, A.; Wang, Y.; Xu, S.; Tang, Y.; Jin, X.; Wang, S.; Qin, L.; Sun, Y.; Fan, C.; Snijder, E.J.; Neuman, B.W.; Chen, Y.; Ahola, T.; Guo, D. Identification and characterization of a ribose 2′-O-methyltransferase encoded by the ronivirus branch of nidovirales. J. Virol., 2016, 90(15), 6675-6685.
[http://dx.doi.org/10.1128/JVI.00658-16] [PMID: 27170751]
[12]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[13]
Ciliberto, G.; Cardone, L. Boosting the arsenal against COVID-19 through computational drug repurposing. Drug Discov. Today, 2020, 25(6), 946-948.
[http://dx.doi.org/10.1016/j.drudis.2020.04.005] [PMID: 32304645]
[14]
Xu, J.; Shi, P-Y.; Li, H.; Zhou, J. Broad spectrum antiviral agent niclosamide and its therapeutic potential. ACS Infect. Dis., 2020, 6(5), 909-915.
[http://dx.doi.org/10.1021/acsinfecdis.0c00052] [PMID: 32125140]
[15]
Brites, C.; Nóbrega, I.; Luz, E.; Travassos, A.G.; Lorenzo, C.; Netto, E.M. Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women. HIV Clin. Trials, 2018, 19(3), 94-100.
[http://dx.doi.org/10.1080/15284336.2018.1459343] [PMID: 29629852]
[16]
Pommier, Y.; Johnson, A.A.; Marchand, C. Integrase inhibitors to treat HIV/AIDS. Nat. Rev. Drug Discov., 2005, 4(3), 236-248.
[http://dx.doi.org/10.1038/nrd1660] [PMID: 15729361]
[17]
Hussaini, S.M.A. Therapeutic significance of quinolines: a patent review (2013-2015). Expert Opin. Ther. Pat., 2016, 26(10), 1201-1221.
[18]
Alexpandi, R.; De Mesquita, J.F.; Pandian, S.K.; Ravi, A.V. Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and spike-RBD-ACE2 inhibitor for drug-repurposing against covid-19: An in silico analysis. Front. Microbiol., 2020, 11, 1796.
[http://dx.doi.org/10.3389/fmicb.2020.01796] [PMID: 32793181]
[19]
Han, Y.; Zhang, J.; Hu, C.Q.; Zhang, X.; Ma, B.; Zhang, P. In silico ADME and toxicity prediction of ceftazidime and its impurities. Front. Pharmacol., 2019, 10, 434.
[http://dx.doi.org/10.3389/fphar.2019.00434] [PMID: 31068821]
[20]
Cada, D.J.; Torres, S.; Levien, T.L.; Baker, D.E. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate tablets. Hosp. Pharm., 2013, 48(1), 48-56.
[http://dx.doi.org/10.1310/hpj4801-48] [PMID: 24421423]
[21]
Mandal, S.; Prathipati, P.K.; Belshan, M.; Destache, C.J. A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection: a proof-of-concept study. Antiviral Res., 2019, 167, 83-88.
[http://dx.doi.org/10.1016/j.antiviral.2019.04.007] [PMID: 30991088]
[22]
Gallant, J.; Lazzarin, A.; Mills, A.; Orkin, C.; Podzamczer, D.; Tebas, P.; Girard, P.M.; Brar, I.; Daar, E.S.; Wohl, D.; Rockstroh, J.; Wei, X.; Custodio, J.; White, K.; Martin, H.; Cheng, A.; Quirk, E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet, 2017, 390(10107), 2063-2072.
[http://dx.doi.org/10.1016/S0140-6736(17)32299-7] [PMID: 28867497]
[23]
Gallant, JE; Thompson, M; DeJesus, E; Voskuhl, GW; Wei, X; Zhang, H Antiviral activity, safety, and pharmacokinetics of bictegravir as 10-day monotherapy in HIV-1-infected adults. J. Acquir. Immune Defic. Syndr., 2017, 75(1), 61.
[24]
Hassounah, S.A.; Alikhani, A.; Oliveira, M.; Bharaj, S.; Ibanescu, R-I.; Osman, N.; Xu, H.T.; Brenner, B.G.; Mesplède, T.; Wainberg, M.A. Antiviral activity of bictegravir and cabotegravir against integrase inhibitor-resistant SIVmac239 and HIV-1. Antimicrob. Agents Chemother., 2017, 61(12), e01695-17.
[http://dx.doi.org/10.1128/AAC.01695-17] [PMID: 28923862]
[25]
Sax, P.E.; DeJesus, E.; Crofoot, G.; Ward, D.; Benson, P.; Dretler, R.; Mills, A.; Brinson, C.; Peloquin, J.; Wei, X.; White, K.; Cheng, A.; Martin, H.; Quirk, E. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV, 2017, 4(4), e154-e160.
[http://dx.doi.org/10.1016/S2352-3018(17)30016-4] [PMID: 28219610]
[26]
Sax, P.E.; Pozniak, A.; Montes, M.L.; Koenig, E.; DeJesus, E.; Stellbrink, H-J.; Antinori, A.; Workowski, K.; Slim, J.; Reynes, J.; Garner, W.; Custodio, J.; White, K.; SenGupta, D.; Cheng, A.; Quirk, E. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet, 2017, 390(10107), 2073-2082.
[http://dx.doi.org/10.1016/S0140-6736(17)32340-1] [PMID: 28867499]
[27]
Khan, R.J.; Jha, R.K.; Amera, G.M.; Jain, M.; Singh, E.; Pathak, A. Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase. J. Biomol. Struct. Dyn., 2020, 39(8), 2679-2692.
[http://dx.doi.org/10.1080/07391102.2020.1753577] [PMID: 32266873]
[28]
Hocqueloux, L.; Raffi, F.; Prazuck, T.; Bernard, L.; Sunder, S.; Esnault, J-L.; Rey, D.; Le Moal, G.; Roncato-Saberan, M.; André, M.; Billaud, E.; Valéry, A.; Avettand-Fènoël, V.; Parienti, J.J.; Allavena, C. Dolutegravir monotherapy versus dolutegravir/abacavir/lamivudine for virologically suppressed people living with chronic human immunodeficiency virus infection: the randomized noninferiority MONotherapy of TiviCAY trial. Clin. Infect. Dis., 2019, 69(9), 1498-1505.
[http://dx.doi.org/10.1093/cid/ciy1132] [PMID: 30601976]
[29]
Cottrell, M.L.; Hadzic, T.; Kashuba, A.D. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin. Pharmacokinet., 2013, 52(11), 981-994.
[http://dx.doi.org/10.1007/s40262-013-0093-2] [PMID: 23824675]
[30]
Min, S.; Song, I.; Borland, J.; Chen, S.; Lou, Y.; Fujiwara, T.; Piscitelli, S.C. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob. Agents Chemother., 2010, 54(1), 254-258.
[http://dx.doi.org/10.1128/AAC.00842-09] [PMID: 19884365]
[31]
Kandel, C.E.; Walmsley, S.L. Dolutegravir - a review of the pharmacology, efficacy, and safety in the treatment of HIV. Drug Des. Devel. Ther., 2015, 9, 3547-3555.
[http://dx.doi.org/10.2147/DDDT.S84850] [PMID: 26185421]
[32]
Kumar, Y.; Singh, H.; Patel, C.N. In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing. J. Infect. Public Health, 2020, 13(9), 1210-1223.
[33]
Beg, M.; Athar, F. Anti-HIV and Anti-HCV drugs are the putative inhibitors of RNA-dependent-RNA polymerase activity of NSP12 of the SARS CoV-2 (COVID-19). Pharm. Pharmacol. Int. J., 2020, 8(3), 163-172.
[http://dx.doi.org/10.15406/ppij.2020.08.00292]
[34]
Beck, B.R.; Shin, B.; Choi, Y.; Park, S.; Kang, K. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput. Struct. Biotechnol. J., 2020, 18(18), 784-790.
[http://dx.doi.org/10.1016/j.csbj.2020.03.025] [PMID: 32280433]
[35]
Md Nayeem, S.; Sohail, E.M.; Srihari, N.V.; Indira, P.; Srinivasa Reddy, M. Target SARS-CoV-2: theoretical exploration on clinical suitability of certain drugs. J. Biomol. Struct. Dyn., 2021, 1-8.
[http://dx.doi.org/10.1080/07391102.2021.1924262] [PMID: 33988066]
[36]
Alavian, G.; Kolahdouzan, K.; Mortezazadeh, M.; Torabi, Z.S. Antiretrovirals for prophylaxis against covid-19: a comprehensive literature review. J. Clin. Pharmacol., 2021, 61(5), 581-590.
[http://dx.doi.org/10.1002/jcph.1788] [PMID: 33217030]
[37]
Cipolat, M.M.; Sprinz, E. COVID-19 pneumonia in an HIV-positive woman on antiretroviral therapy and undetectable viral load in Porto Alegre, Brazil. Braz. J. Infect. Dis., 2020, 24(5), 455-457.
[http://dx.doi.org/10.1016/j.bjid.2020.07.009] [PMID: 32866436]
[38]
Mouscadet, J-F.; Tchertanov, L. Raltegravir: molecular basis of its mechanism of action. Eur. J. Med. Res., 2009, 14(S3)(Suppl. 3), 5-16.
[http://dx.doi.org/10.1186/2047-783X-14-S3-5] [PMID: 19959411]
[39]
Moreira, F.L.; Marques, M.P.; Duarte, G.; Lanchote, V.L. Determination of raltegravir and raltegravir glucuronide in human plasma and urine by LC-MS/MS with application in a maternal-fetal pharmacokinetic study. J. Pharm. Biomed. Anal., 2020, 177, 112838.
[http://dx.doi.org/10.1016/j.jpba.2019.112838] [PMID: 31525573]
[40]
Daoud, S.; Alabed, S.J.; Dahabiyeh, L.A. Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies. Acta Pharm., 2021, 71(2), 163-174.
[http://dx.doi.org/10.2478/acph-2021-0016] [PMID: 33151166]
[41]
Tazikeh-Lemeski, E.; Moradi, S.; Raoufi, R.; Shahlaei, M.; Janlou, M.A.M.; Zolghadri, S. Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study. J. Biomol. Struct. Dyn., 2020, 39(13), 4633-4646.
[PMID: 32573355]
[42]
Wei, T.Z.; Wang, H.; Wu, X.Q.; Lu, Y.; Guan, S.H.; Dong, F.Q.; Dong, C.L.; Zhu, G.L.; Bao, Y.Z.; Zhang, J.; Wang, G.Y.; Li, H.Y. In silico screening of potential spike glycoprotein inhibitors of SARS-CoV-2 with drug repurposing strategy. Chin. J. Integr. Med., 2020, 26(9), 663-669.
[http://dx.doi.org/10.1007/s11655-020-3427-6] [PMID: 32740825]
[43]
Toor, H.G.; Banerjee, D.I.; Lipsa Rath, S.; Darji, S.A. Computational drug re-purposing targeting the spike glycoprotein of SARS-CoV-2 as an effective strategy to neutralize COVID-19. Eur. J. Pharmacol., 2021, 890, 173720.
[http://dx.doi.org/10.1016/j.ejphar.2020.173720] [PMID: 33160938]

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