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ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Research Article

In-Silico Structure-Based Drug Discovery of Candidate Drugs against Novel Protein Receptor Complex Nsp10-Nsp16 of SARS-CoV-2 using Drug Repurposing Approach

Author(s): Abhishek Sengupta, Pooja Vijayaraghavan, Priyansh Srivastava, Lovely Gupta, Chaitanya Chandwani and Priyanka Narad*

Volume 2, Issue 2, 2021

Published on: 14 October, 2020

Page: [255 - 264] Pages: 10

DOI: 10.2174/2666796701999201014161604


Background: Several therapeutic possibilities have been explored against Severe Acute Respiratory Syndrome-2 (SARS-CoV-2), such as convalescent plasma (CP), intravenous immunoglobulin (IVIG) and monoclonal antibodies. Compounds such as hydroxychloroquine have also been found to have fatal drawbacks. Repurposing of existing antiviral drugs can be an effective strategy, which could fasten up the process of drug discovery.

Objective: The present study is designed to predict the computational efficacy of pre-existing antiviral drugs as inhibitors for the Nsp10-Nsp16 complex protein of SARS-CoV-2.

Methods: Twenty-six known antiviral drugs along with their similar structures based on Tanimoto similarity, were screened towards the Nsp10-Nsp16 complex’s active site.

Results: Our study reports competitive binding of 1-[3-[2-(2-Ethoxyphenoxy) ethylamino]-2- hydroxypropyl] -9H-carbazol-4-ol against AdoMet binding site in Nsp10-Nsp16 complex. Formation of the stable ligand-receptor complex with 1-[3-[2-(2-Ethoxyphenoxy) ethylamino]-2-hydroxypropyl] -9Hcarbazol- 4-ol could functionally inhibit the Nsp10-Nsp16 complex, thereby making the SARS-CoV-2 vulnerable to host immuno-surveillance mechanisms.

Conclusion: We conclude that these computational hits can display positive results in in-vitro trials against SARS-CoV-2.

Keywords: SARS-CoV-2, Nsp10-Nsp16 complex, virtual screening, molecular docking, ADME prediction, COVID-19.

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
[] [PMID: 32007143]
World Health Organization, Coronavirus disease 2019 (COVID-19) Situation Report – 88 Available from:
Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020; 395(10223): 470-3.
[] [PMID: 31986257]
Dai W, Zhang B, Jiang XM, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 2020; 368(6497): 1331-5.
[] [PMID: 32321856]
Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov Today 2020; 25(4): 668-88.
[] [PMID: 32006468]
Zhu N, Zhang D, Wang W, et al. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in 260 China. N Engl J Med 2020; 382(8): 727-33.
[] [PMID: 31978945]
Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579(7798): 265-9.
[] [PMID: 32015508]
Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 2020; 92(4): 418-23.
[] [PMID: 31967327]
Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
[] [PMID: 25720466]
Amin A, Ghosh K, Gayen S, Jha T. Chemical-informatics approach to COVID-19 drug discovery: Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papainlike protease (PLpro) inhibitors. J Biomol Struct Dyn 2020; 2020: 1-10.
Goyal B, Goyal D. Targeting the dimerization of the main protease of coronaviruses: a potential broad-spectrum therapeutic strategy. ACS Comb Sci 2020; 22(6): 297-305.
[] [PMID: 32402186]
Northwestern Medicine, Northwestern University Available from:
von Grotthuss M, Wyrwicz LS, Rychlewski L. mRNA cap-1 methyltransferase in the SARS genome. Cell 2003; 113(6): 701-2.
[] [PMID: 12809601]
Masters PS. The molecular biology of coronaviruses. Adv Virus Res 2006; 66: 193-292.
[] [PMID: 16877062]
Bouvet M, Debarnot C, Imbert I, et al. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog 2010; 6(4)e1000863
[] [PMID: 20421945]
Shuman S. Structure, mechanism, and evolution of the mRNA capping apparatus. Prog Nucleic Acid Res Mol Biol 2001; 66: 1-40.
[PMID: 11051760]
Gu M, Lima CD. Processing the message: structural insights into capping and decapping mRNA. Curr Opin Struct Biol 2005; 15(1): 99-106.
[] [PMID: 15718140]
Shuman S. What messenger RNA capping tells us about eukaryotic evolution. Nat Rev Mol Cell Biol 2002; 3(8): 619-25.
[] [PMID: 12154373]
Yoneyama M, Fujita T. Recognition of viral nucleic acids in innate immunity. Rev Med Virol 2010; 20(1): 4-22.
[] [PMID: 20041442]
Voitenko OS, Dhroso A, Feldmann A, Korkin D, Kalinina OV. Patterns of amino acid conservation in human and animal immunodeficiency viruses. Bioinformatics 2016; 32(17): i685-92.
[] [PMID: 27587690]
Bujnicki JM, Rychlewski L. In silico identification, structure prediction and phylogenetic analysis of the 2′-O-ribose (cap 1) methyltransferase domain in the large structural protein of ssRNA negative-strand viruses. Protein Eng 2002; 15(2): 101-8.
[] [PMID: 11917146]
Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B. An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J 2002; 21(11): 2757-68.
[] [PMID: 12032088]
Ferron F, Longhi S, Henrissat B, Canard B. Viral RNA-polymerases -- a predicted 2′-O-ribose methyltransferase domain shared by all mononegavirales. Trends Biochem Sci 2002; 27(5): 222-4.
[] [PMID: 12076527]
Martin JL, McMillan FM. SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol 2002; 12(6): 783-93.
[] [PMID: 12504684]
Snijder EJ, Bredenbeek PJ, Dobbe JC, et al. 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.
[] [PMID: 12927536]
Decroly E, Debarnot C, Ferron F, et al. Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2′-O-methyltransferase nsp10/nsp16 complex. PLoS Pathog 2011; 7(5)e1002059
[] [PMID: 21637813]
Amin SA, Jha T. Fight against novel coronavirus: a perspective of medicinal chemists. Eur J Med Chem 2020; 201112559
[] [PMID: 32563814]
Kim S, Thiessen PA, Bolton EE, et al. Substance and compound databases. Nucleic Acids Res 2016; 44(D1): D1202-13.
[] [PMID: 26400175]
Schrödinger, QikProp Available from:
Ntie-Kang F. An in silico evaluation of the ADMET profile of the StreptomeDB database. Springerplus 2013; 2(1): 353.
[] [PMID: 23961417]
Srivastava P, Pal R, Misra G. In: Comparative modelling and virtual screening to discover potential competitive inhibitors targeting the 30s ribosomal subunit S2 and S9 in Acinetobacter baumannii, International Conference on Bioinformatics and Systems Biology (BSB). Allahabad, India. October 26-28; IEEE 2018..
Schrödinger, LigPrep Available from:
Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res 2000; 28(1): 235-42.
[] [PMID: 10592235]
Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 2013; 27(3): 221-34.
[] [PMID: 23579614]
Protein Preparation Wizard, Schrödinger. Available from:.
Geourjon C, Deléage G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci 1995; 11(6): 681-4.
[] [PMID: 8808585]
Schrödinger, Glide Available from:
Tyagi S, Saxena S, Srivastava P, et al. Screening the binding potential of quercetin with parallel, antiparallel and mixed G-quadruplexes of human telomere and cancer protooncogenes using molecular docking approach. SN Applied Sci 2020; 2(3): 490.
Li J, Abel R, Zhu K, Cao Y, Zhao S, Friesner RA. The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins 2011; 79(10): 2794-812.
[] [PMID: 21905107]
Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009; 459(7249): 931-9.
[] [PMID: 19525932]
Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. NSR 2020; 7(6): 1012-23.
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(14): 14.
[] [PMID: 32194980]

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