Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Potential Candidates against COVID-19 Targeting RNA-Dependent RNA Polymerase: A Comprehensive Review

Author(s): Neetu Agrawal and Ahsas Goyal*

Volume 23, Issue 3, 2022

Published on: 21 April, 2021

Page: [396 - 419] Pages: 24

DOI: 10.2174/1389201022666210421102513

Price: $65

Abstract

Due to the extremely contagious nature of SARS-COV-2, it presents a significant threat to humans worldwide. A plethora of studies are going on all over the world to discover the drug to fight SARS-COV-2. One of the most promising targets is RNA-dependent RNA polymerase (RdRp), responsible for viral RNA replication in host cells. Since RdRp is a viral enzyme with no host cell homologs, it allows the development of selective SARS-COV-2 RdRp inhibitors. A variety of studies used in silico approaches for virtual screening, molecular docking, and repurposing of already existing drugs and phytochemicals against SARS-COV-2 RdRp. This review focuses on collating compounds possessing the potential to inhibit SARS-COV-2 RdRp based on in silico studies to give medicinal chemists food for thought so that the existing drugs can be repurposed for the control and treatment of ongoing COVID-19 pandemic after performing in vitro and in vivo experiments.

Keywords: COVID-19, SARS-COV-2, in silico, molecular docking, RdRp, RNA-dependent RNA polymerase.

« Previous Next »
Graphical Abstract

[1]
COVID live - Coronavirus statistics - worldometer Available at:. https://www.worldometers.info/coronavirus/?utm_ campaign=homeAdUOA?Si
[2]
Jiang, S.; Shi, Z.; Shu, Y.; Song, J.; Gao, G.F.; Tan, W.; Guo, D. A distinct name is needed for the new coronavirus. Lancet, 2020, 395(10228), 949.
[http://dx.doi.org/10.1016/S0140-6736(20)30419-0] [PMID: 32087125]
[3]
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]
[4]
Alazmi, M.; Motwalli, O. In silico virtual screening, characterization, docking and molecular dynamics studies of crucial SARS-CoV-2 proteins. J. Biomol. Struct. Dyn., 2020, 1-11.
[http://dx.doi.org/10.1080/07391102.2020.1803965] [PMID: 32762537]
[5]
Durmuş, S.; Ülgen, K.Ö. Comparative interactomics for virus-human protein-protein interactions: DNA viruses versus RNA viruses. FEBS Open Bio, 2017, 7(1), 96-107.
[http://dx.doi.org/10.1002/2211-5463.12167] [PMID: 28097092]
[6]
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]
[7]
Elfiky, A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci., 2020, 253117592
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[8]
Gao, Y.; Yan, L.; Huang, Y.; Liu, F.; Zhao, Y.; Cao, L.; Wang, T.; Sun, Q.; Ming, Z.; Zhang, L.; Ge, J.; Zheng, L.; Zhang, Y.; Wang, H.; Zhu, Y.; Zhu, C.; Hu, T.; Hua, T.; Zhang, B.; Yang, X.; Li, J.; Yang, H.; Liu, Z.; Xu, W.; Guddat, L.W.; Wang, Q.; Lou, Z.; Rao, Z. Z. Structure of the rna-dependent rna polymerase from COVID-19 Virus. Science (80-. ), 2020, 368, 779-782..
[9]
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 (80-. ), 2020, 368, 779-782.,
[10]
Gordon, C.J.; Tchesnokov, E.P.; Woolner, E.; Perry, J.K.; Feng, J.Y.; Porter, D.P.; Götte, M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J. Biol. Chem., 2020, 295(20), 6785-6797.
[http://dx.doi.org/10.1074/jbc.RA120.013679] [PMID: 32284326]
[11]
Chaudhary, K.K.; Mishra, N. A Review on Molecular Docking: Novel Tool for Drug Discovery. JSM Chem., 2016, 4, 1029.
[12]
Aftab, S.O.; Ghouri, M.Z.; Masood, M.U.; Haider, Z.; Khan, Z.; Ahmad, A.; Munawar, N. Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach. J. Transl. Med., 2020, 18(1), 275.
[http://dx.doi.org/10.1186/s12967-020-02439-0] [PMID: 32635935]
[13]
Ahmad, M.; Dwivedy, A.; Mariadasse, R.; Tiwari, S.; Kar, D.; Jeyakanthan, J.; Biswal, B.K. Prediction of small molecule inhibitors targeting the severe acute respiratory syndrome coronavirus-2 rna-dependent rna polymerase. ACS Omega, 2020, 5(29), 18356-18366.
[http://dx.doi.org/10.1021/acsomega.0c02096] [PMID: 32743211]
[14]
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.
[PMID: 32720571]
[15]
Elfiky, A.A. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective. J. Biomol. Struct. Dyn., 2020, 1-9.
[PMID: 32338164]
[16]
Elfiky, A.A. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci., 2020, 248117477
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[17]
Elfiky, A.A. Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials. J. Med. Virol., 2016, 88(12), 2044-2051.
[http://dx.doi.org/10.1002/jmv.24678] [PMID: 27604059]
[18]
Lung, J.; Lin, Y.S.; Yang, Y.H.; Chou, Y.L.; Shu, L.H.; Cheng, Y.C.; Liu, H.T.; Wu, C.Y. The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase. J. Med. Virol., 2020, 92(6), 693-697.
[http://dx.doi.org/10.1002/jmv.25761] [PMID: 32167173]
[19]
Parvez, M.S.A.; Karim, M.A.; Hasan, M.; Jaman, J.; Karim, Z.; Tahsin, T.; Hasan, M.N.; Hosen, M.J. Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach. Int. J. Biol. Macromol., 2020, 163, 1787-1797.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.09.098] [PMID: 32950529]
[20]
Quimque, M.T.J.; Notarte, K.I.R.; Fernandez, R.A.T.; Mendoza, M.A.O.; Liman, R.A.D.; Lim, J.A.K.; Pilapil, L.A.E.; Ong, J.K.H.; Pastrana, A.M.; Khan, A.; Wei, D.Q.; Macabeo, A.P.G. Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms. J. Biomol. Struct. Dyn., 2020, 1-18.
[http://dx.doi.org/10.1080/07391102.2020.1776639] [PMID: 32476574]
[21]
Alamri, M.A.; Altharawi, A.; Alabbas, A.B.; Alossaimi, M.A.; Alqahtani, S.M. Structure-Based Virtual Screening and Molecular Dynamics of Phytochemicals Derived from Saudi Medicinal Plants to Identify Potential COVID-19 Therapeutics. Arab. J. Chem., 2020, 13, 7224-7234.
[http://dx.doi.org/10.1016/j.arabjc.2020.08.004]
[22]
da Silva, F.M.A.; da Silva, K.P.A.; de Oliveira, L.P.M.; Costa, E.V.; Koolen, H.H.F.; Pinheiro, M.L.B.; de Souza, A.Q.L.; de Souza, A.D.L. Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). Mem. Inst. Oswaldo Cruz, 2020, 115e200207
[http://dx.doi.org/10.1590/0074-02760200207] [PMID: 33027419]
[23]
Gutierrez-Villagomez, J.M.; Campos-García, T.; Molina-Torres, J.; López, M.G.; Vázquez-Martínez, J. Alkamides and piperamides as potential antivirals against the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). J. Phys. Chem. Lett., 2020, 11(19), 8008-8016.
[http://dx.doi.org/10.1021/acs.jpclett.0c01685] [PMID: 32840378]
[24]
Kar, P.; Sharma, N.R.; Singh, B.; Sen, A.; Roy, A. Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: An in silico investigation. J. Biomol. Struct. Dyn., 2020, 1-12.
[PMID: 32552595]
[25]
Khan, A.; Khan, M.; Saleem, S.; Babar, Z.; Ali, A.; Khan, A.A.; Sardar, Z.; Hamayun, F.; Ali, S.S.; Wei, D.Q. Phylogenetic analysis and structural perspectives of rna-dependent rna-polymerase inhibition from sars-cov-2 with natural products. Interdiscip. Sci., 2020, 12(3), 335-348.
[http://dx.doi.org/10.1007/s12539-020-00381-9] [PMID: 32617855]
[26]
Sharma, A.; Vora, J.; Patel, D.; Sinha, S.; Jha, P.C.; Shrivastava, N. Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches. J. Biomol. Struct. Dyn., 2020, 1-16.
[http://dx.doi.org/10.1080/07391102.2020.1846624] [PMID: 33183178]
[27]
Silva, J.K.R.D.; Figueiredo, P.L.B.; Byler, K.G.; Setzer, W.N. essential oils as antiviral agents. Potential of essential oils to treat sars-cov-2 infection: an in-silico investigation. Int. J. Mol. Sci., 2020, 21(10), 3426.
[http://dx.doi.org/10.3390/ijms21103426] [PMID: 32408699]
[28]
Singh, S.; Sk, M.F.; Sonawane, A.; Kar, P.; Sadhukhan, S. Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. J. Biomol. Struct. Dyn., 2020, 1-16.
[http://dx.doi.org/10.1080/07391102.2020.1796810] [PMID: 32720577]
[29]
Vardhan, S.; Sahoo, S.K. In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Comput. Biol. Med., 2020, 124103936
[http://dx.doi.org/10.1016/j.compbiomed.2020.103936] [PMID: 32738628]
[30]
Vijayakumar, B.G.; Ramesh, D.; Joji, A.; Jayachandra Prakasan, J.; Kannan, T. In silico pharmacokinetic and molecular docking studies of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-CoV-2. Eur. J. Pharmacol., 2020, 886173448
[http://dx.doi.org/10.1016/j.ejphar.2020.173448] [PMID: 32768503]
[31]
Baby, K.; Maity, S.; Mehta, C.H.; Suresh, A.; Nayak, U.Y.; Nayak, Y. Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19. F1000 Res., 2020, 9, 1166.
[http://dx.doi.org/10.12688/f1000research.26359.1] [PMID: 33204411]
[32]
Barage, S.; Karthic, A.; Bavi, R.; Desai, N.; Kumar, R.; Kumar, V.; Lee, K.W. Identification and characterization of novel RdRp and Nsp15 inhibitors for SARS-COV2 using computational approach. J. Biomol. Struct. Dyn., 2020, 1-18.
[http://dx.doi.org/10.1080/07391102.2020.1841026] [PMID: 33155531]
[33]
Chowdhury, T.; Roymahapatra, G.; Mandal, S.M. In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases. Infect. Disord. Drug Targets, 2020, 20, 1-11.
[http://dx.doi.org/10.2174/1871526520666200727153643] [PMID: 32718300]
[34]
Gul, S.; Ozcan, O.; Asar, S.; Okyar, A.; Barıs, I.; Kavakli, I.H. In silico identification of widely used and well-tolerated drugs as potential SARS-CoV-2 3C-like protease and viral RNA-dependent RNA polymerase inhibitors for direct use in clinical trials. J. Biomol. Struct. Dyn., 2020, 1-20.
[http://dx.doi.org/10.1080/07391102.2020.1802346] [PMID: 32752938]
[35]
Iftikhar, H.; Ali, H.N.; Farooq, S.; Naveed, H.; Shahzad-Ul-Hussan, S. Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach. Comput. Biol. Med., 2020, 122103848
[http://dx.doi.org/10.1016/j.compbiomed.2020.103848] [PMID: 32658735]
[36]
Mutlu, O.; Ugurel, O.M.; Sariyer, E.; Ata, O.; Inci, T.G.; Ugurel, E.; Kocer, S.; Turgut-Balik, D. Targeting SARS-CoV-2 Nsp12/Nsp8 interaction interface with approved and investigational drugs: An in silico structure-based approach. J. Biomol. Struct. Dyn., 2020, 1-13.
[http://dx.doi.org/10.1080/07391102.2020.1819882] [PMID: 32933378]
[37]
Pokhrel, R.; Chapagain, P.; Siltberg-Liberles, J. Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2. J. Med. Microbiol., 2020, 69(6), 864-873.
[http://dx.doi.org/10.1099/jmm.0.001203] [PMID: 32469301]
[38]
Thurakkal, L.; Singh, S.; Roy, R.; Kar, P.; Sadhukhan, S.; Porel, M. An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets. Chem. Phys. Lett., 2021, 763138193
[http://dx.doi.org/10.1016/j.cplett.2020.138193] [PMID: 33223560]
[39]
Zhao, Z.; Bourne, P.E. Structural insights into the binding modes of viral RNA-Dependent RNA polymerases using a function-site interaction fingerprint method for RNA virus drug discovery. J. Proteome Res., 2020, 19(11), 4698-4705.
[http://dx.doi.org/10.1021/acs.jproteome.0c00623] [PMID: 32946692]
[40]
Murugan, N.A.; Kumar, S.; Jeyakanthan, J.; Srivastava, V. Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach. Sci. Rep., 2020, 10(1), 19125.
[http://dx.doi.org/10.1038/s41598-020-75762-7] [PMID: 33154404]
[41]
Sahu, B.; Behera, S.K.; Das, R.; Dalvi, T.; Chowdhury, A.; Dewangan, B.; Kalia, K.; Shard, A. Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19. Curr. Comput. Aided. Drug Des., 2020, 16, 1-15.

Rights & Permissions Print Cite
Article Metrics
29
4
© 2024 Bentham Science Publishers | Privacy Policy