Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Mini-Review Article

A Review on the New Indication of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in the Treatment of Coronavirus Disease 2019

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

Volume 22, Issue 5, 2022

Published on: 11 April, 2022

Article ID: e180222201281 Pages: 6

DOI: 10.2174/1871526522666220218115617

Price: $65

Abstract

Background: In December 2019, a new coronavirus (nCoV) emerged as a public health concern spreading all around the world. Several attempts have been made to discover effective drugs and vaccines. Up to now, multiple COVID-19 vaccines have been developed against this mysterious virus, and a lot of individuals have already got vaccinated.

Objective: Anti-viral drugs are effective in treating and managing COVID-19. Nucleoside reverse transcriptase inhibitors (NRTIs) are a collection of antiviral drugs for treating HIV and HBV infections. These drugs prevent virus replication by blocking reverse transcriptase (RT). In this review, we discuss the interaction of this class of anti- HIV drugs with specific functional proteins and enzymes of SARSCoV- 2.

Methods: A search of the databases, including Web of Science, Embase, PubMed, Scopus, and Google Scholar, was conducted from commencement to September 2020. The relevant articles on the potential effects of NRTIs on COVID-19 were collected. Finally, twenty-three articles were selected, including all in vitro, in vivo, and clinical studies.

Results: It was observed that RdRp, spike, ACE2, PNP, inflammatory cytokines, and nucleocapsid protein participate in the pathogenesis of SARS-CoV-2. NRTIs target these proteins by binding to them.

Conclusion: This review is focused on the mechanisms of NRTIs to introduce them as potential therapies for COVID-19. However, further in vitro and in vivo investigations will provide helpful information for the identification of drug candidates as a part of COVID-19 management.

Keywords: Coronavirus, SARS-CoV-2, COVID-19, RdRp, nucleoside reverse transcriptase inhibitors, zidovudine.

Graphical Abstract

[1]
Borgio JF, Alsuwat HS, Al Otaibi WM, et al. State-of-the-art tools unveil potent drug targets amongst clinically approved drugs to inhibit helicase in SARS-CoV-2. Arch Med Sci 2020; 16(3): 508-18.
[http://dx.doi.org/10.5114/aoms.2020.94567] [PMID: 32399096]
[2]
Bogoch II, Watts A, Thomas-Bachli A, Huber C, Kraemer MU, Khan K. Pneumonia of unknown aetiology in Wuhan, China: Potential for international spread via commercial air travel. J Travel Med 2020; 27(2): taaa008.
[PMID: 31943059]
[3]
Sharma O, Sultan AA, Ding H, Triggle CR. A review of the progress and challenges of developing a vaccine for COVID-19. Front Immunol 2020; 11: 585354.
[http://dx.doi.org/10.3389/fimmu.2020.585354] [PMID: 33163000]
[4]
Hui DSI, Azhar E, Madani TA, et al. 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: 264-6.
[http://dx.doi.org/10.1016/j.ijid.2020.01.009] [PMID: 31953166]
[5]
Baluku JB, Mwebaza S, Ingabire G, Nsereko C, Muwanga M. HIV and SARS-CoV-2 coinfection: A case report from Uganda. J Med Virol 2020; 92(11): 2351-3.
[http://dx.doi.org/10.1002/jmv.26044] [PMID: 32437000]
[6]
Rui L, Haonan L, Wanyi C. Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation. Biophys Chem 2020; 267: 106472.
[http://dx.doi.org/10.1016/j.bpc.2020.106472] [PMID: 32916377]
[7]
Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci 2020; 253: 117592.
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[8]
Hasan A, Paray BA, Hussain A, et al. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J Biomol Struct Dyn 2021; 39(8): 3025-33.
[http://dx.doi.org/10.1080/07391102.2020.1754293] [PMID: 32274964]
[9]
Peng Q, Peng R, Yuan B, et al. Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2. Cell Rep 2020; 31(11): 107774.
[http://dx.doi.org/10.1016/j.celrep.2020.107774] [PMID: 32531208]
[10]
Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn 2021; 39(9): 3409-18.
[PMID: 32306836]
[11]
Pandey P, Khan F, Rana AK, Srivastava Y, Jha SK, Jha NK. A drug repurposing approach towards elucidating the potential of flavonoids as COVID-19 spike protein inhibitors. Biointerface Res Appl Chem 2021; 11(1): 8482-501.
[12]
Abd-Elsalam S, Noor RA, Badawi R, et al. Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study. J Med Virol 2021; 93(10): 5833-8.
[http://dx.doi.org/10.1002/jmv.27122] [PMID: 34076901]
[13]
Abd-Elsalam S, Ahmed OA, Mansour NO, et al. Remdesivir efficacy in COVID-19 treatment: A randomized controlled trial. Am J Trop Med Hyg 2021; 106(3): 886-90.
[http://dx.doi.org/10.4269/ajtmh.21-0606] [PMID: 34649223]
[14]
Dabbous HM, Abd-Elsalam S, El-Sayed MH, et al. Efficacy of favipiravir in COVID-19 treatment: A multi-center randomized study. Arch Virol 2021; 166(3): 949-54.
[http://dx.doi.org/10.1007/s00705-021-04956-9] [PMID: 33492523]
[15]
El-Bendary M, Abd-Elsalam S, Elbaz T, et al. Efficacy of combined sofosbuvir and daclatasvir in the treatment of COVID-19 patients with pneumonia: A multicenter Egyptian study. Expert Rev Anti Infect Ther 2021; 1-5.
[http://dx.doi.org/10.1080/14787210.2021.1950532] [PMID: 34225541]
[16]
Ghazy RM, Almaghraby A, Shaaban R, et al. A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment. Sci Rep 2020; 10(1): 22139.
[http://dx.doi.org/10.1038/s41598-020-77748-x] [PMID: 33335141]
[17]
Rocco PRM, Silva PL, Cruz FF, et al. SARITA-2 investigators Early use of nitazoxanide in mild COVID-19 disease: Randomised, placebo-controlled trial. Eur Respir J 2021; 58(1): 2003725.
[http://dx.doi.org/10.1183/13993003.03725-2020] [PMID: 33361100]
[18]
Verdugo-Paiva F, Izcovich A, Ragusa M, Rada G. Lopinavir-ritonavir for COVID-19: A living systematic review. Medwave 2020; 20(6): e7967.
[http://dx.doi.org/10.5867/medwave.2020.06.7966] [PMID: 32678815]
[19]
Mehta KG, Patel T, Chavda PD, Patel P. Efficacy and safety of colchicine in COVID-19: A meta-analysis of randomised controlled trials. RMD Open 2021; 7(3): e001746.
[http://dx.doi.org/10.1136/rmdopen-2021-001746] [PMID: 34810227]
[20]
Choi H, Shin E-C. Roles of type i and iii interferons in COVID-19. Yonsei Med J 2021; 62(5): 381-90.
[http://dx.doi.org/10.3349/ymj.2021.62.5.381] [PMID: 33908208]
[21]
Cano EJ, Fonseca Fuentes X, Corsini Campioli C, et al. Impact of corticosteroids in coronavirus disease 2019 outcomes: Systematic review and meta-analysis. Chest 2021; 159(3): 1019-40.
[http://dx.doi.org/10.1016/j.chest.2020.10.054] [PMID: 33129791]
[22]
Aziz M, Haghbin H, Abu Sitta E, et al. Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis. J Med Virol 2021; 93(3): 1620-30.
[http://dx.doi.org/10.1002/jmv.26509] [PMID: 32918755]
[23]
Parang K, El-Sayed NS, Kazeminy AJ, Tiwari RK. Comparative antiviral activity of remdesivir and anti-HIV nucleoside analogs against human coronavirus 229E (HCoV-229E). Molecules 2020; 25(10): 2343.
[http://dx.doi.org/10.3390/molecules25102343] [PMID: 32429580]
[24]
Min JS, Kim G-W, Kwon S, Jin Y-H. A cell-based reporter assay for screening inhibitors of MERS coronavirus RNA-dependent RNA polymerase activity. J Clin Med 2020; 9(8): 2399.
[http://dx.doi.org/10.3390/jcm9082399] [PMID: 32727069]
[25]
Jockusch S, Tao C, Li X, et al. A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19. Antiviral Res 2020; 180: 104857.
[http://dx.doi.org/10.1016/j.antiviral.2020.104857] [PMID: 32562705]
[26]
Selisko B, Papageorgiou N, Ferron F, Canard B. Structural and functional basis of the fidelity of nucleotide selection by flavivirus RNA-dependent RNA polymerases. Viruses 2018; 10(2): 59.
[http://dx.doi.org/10.3390/v10020059] [PMID: 29385764]
[27]
Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem 2020; 295(15): 4773-9.
[http://dx.doi.org/10.1074/jbc.AC120.013056] [PMID: 32094225]
[28]
Ju J, Li X, Kumar S, et al. Nucleotide analogues as inhibitors of SARS-CoV Polymerase. Pharmacol Res Perspect 2020; 8(6): e00674.
[http://dx.doi.org/10.1002/prp2.674] [PMID: 33124786]
[29]
Elfiky AA. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: An in silico perspective. J Biomol Struct Dyn 2021; 39(9): 3204-12.
[PMID: 32338164]
[30]
Härter G, Spinner CD, Roider J, et al. COVID-19 in people living with human immunodeficiency virus: A case series of 33 patients. Infection 2020; 48(5): 681-6.
[http://dx.doi.org/10.1007/s15010-020-01438-z] [PMID: 32394344]
[31]
Bailly C, Vergoten G. Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome? Pharmacol Ther 2020; 214: 107618.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107618] [PMID: 32592716]
[32]
Borobia AM, Carcas AJ, Arnalich F, et al. A cohort of patients with COVID-19 in a major teaching hospital in Europe. J Clin Med 2020; 9(6): 1733.
[http://dx.doi.org/10.3390/jcm9061733] [PMID: 32512688]
[33]
Del Amo J, Polo R, Moreno S, et al. The Spanish HIV/COVID-19 Collaboration Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy: A cohort study. Ann Intern Med 2020; 173(7): 536-41.
[http://dx.doi.org/10.7326/M20-3689] [PMID: 32589451]
[34]
Park S-J, Yu K-M, Kim Y-I, et al. Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets. MBio 2020; 11(3): e01114-20.
[http://dx.doi.org/10.1128/mBio.01114-20] [PMID: 32444382]
[35]
Wu F, Wang A, Liu M, Wang Q, Chen J, Xia S, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications 2020.
[http://dx.doi.org/10.2139/ssrn.3566211]
[36]
Chien M, Anderson TK, Jockusch S, et al. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase, a key drug target for COVID-19. J Proteome Res 2020; 19(11): 4690-7.
[http://dx.doi.org/10.1021/acs.jproteome.0c00392] [PMID: 32692185]
[37]
Cava C, Bertoli G, Castiglioni I. In silico discovery of candidate drugs against Covid-19. Viruses 2020; 12(4): 404.
[http://dx.doi.org/10.3390/v12040404] [PMID: 32268515]
[38]
Zhao D-C, Li Y-M, Ma J-L, et al. Single-cell RNA sequencing reveals distinct gene expression patterns in glucose metabolism of human preimplantation embryos. Reprod Fertil Dev 2019; 31(2): 237-47.
[http://dx.doi.org/10.1071/RD18178] [PMID: 30017025]
[39]
Zhou L, Wang J, Liu G, et al. Probing antiviral drugs against SARS-CoV-2 through virus-drug association prediction based on the KATZ method. Genomics 2020; 112(6): 4427-34.
[http://dx.doi.org/10.1016/j.ygeno.2020.07.044] [PMID: 32745502]
[40]
Alakwaa FM. Repurposing didanosine as a potential treatment for COVID-19 using single-cell RNA sequencing data. mSystems 2020; 5(2): e00297-20.
[http://dx.doi.org/10.1128/mSystems.00297-20] [PMID: 32291351]
[41]
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev 2020; 54: 62-75.
[http://dx.doi.org/10.1016/j.cytogfr.2020.06.001] [PMID: 32513566]
[42]
Huang C, Wang Y, Li X, et al. 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]
[43]
Melchjorsen J, Risør MW, Søgaard OS, et al. Tenofovir selectively regulates production of inflammatory cytokines and shifts the IL-12/IL-10 balance in human primary cells. J Acquir Immune Defic Syndr 2011; 57(4): 265-75.
[http://dx.doi.org/10.1097/QAI.0b013e3182185276] [PMID: 21471820]
[44]
Yadav R, Imran M, Dhamija P, Suchal K, Handu S. Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2. J Biomol Struct Dyn 2020; 39(12): 4433-48.
[PMID: 32568013]
[45]
Cong Y, Ulasli M, Schepers H, et al. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle. J Virol 2020; 94(4): e01925-19.
[http://dx.doi.org/10.1128/JVI.01925-19] [PMID: 31776274]
[46]
O’Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain RA. SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drug-repurposing. BioRxiv 2020.
[47]
Frediansyah A, Tiwari R, Sharun K, Dhama K, Harapan H. Antivirals for COVID-19: A critical review. Clin Epidemiol Glob Health 2021; 9: 90-8.
[http://dx.doi.org/10.1016/j.cegh.2020.07.006] [PMID: 33521390]

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