In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV
Inemesit A Udofia, Kofoworola O Gbayo, Oluwakemi A Oloba-Whenu, Taofeek B Ogunbayo, Chukwuemeka Isanbor
Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2
An outbreak of a cluster of viral pneumonia cases, subsequently identified as coronavirus disease 2019 , due to a novel SARS-CoV-2 necessitates an urgent need for a vaccine to prevent infection or an approved medication for a cure. In our in silico molecular docking study, a total of 173 compounds, including FDA-approved antiviral drugs, with good ADME descriptors, and some other nucleotide analogues were screened. The results show that these compounds demonstrate strong binding affinity for the residues at the active sites of RNA-dependent RNA-polymerase (RdRp) modelled structures and Chymotrypsin-like cysteine protease (3CLpro) of the HCoV proteins. Free energies (ΔG's) of binding for SARS-CoV-2 and SARS-CoV RdRp range from -5.4 to -8.8 kcal/mol and -4.9 to -8.7 kcal/mol, respectively. Also, SARS-CoV-2 and SARS-CoV 3CLpro gave ΔG values ranging from − 5.1 to − 8.4 kcal/mol and − 5.5 to − 8.6 kcal/mol, respectively. Interesting results are obtained for ivermectin, an antiparasitic agent with broad spectrum activity, which gave the highest binding energy value (− 8.8 kcal/mol) against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2. The reason for such high binding energy values is probably due to the presence of hydroxy, methoxy and sugar moieties in its structure. The stability of the protein-ligand complexes of polymerase inhibitors considered in this investigation, such as Sofosbuvir, Remdesivir, Tenofovir, Ribavirin, Galidesivir, 5c3, 5h1 and 7a1, show strong to moderate hydrogen bonding and hydrophobic interactions (π-π stacked, π-π T-shaped, π-sigma and π-alkyl). The stability provided from such interactions translate into greater antiviral activity or inhibitory effect of the ligands. Assessment of the average free energies of binding of the FDA approved drugs are highly comparable for conformers of a particular inhibitor, indicating similar modes of binding within the pockets.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s13721-021-00299-2.
References
Bajji, Davis, Synthesis and biophysical characterization of tRNALys,3 anticodon stem-loop RNAs containing the mcm5s2U nucleoside, Org Lett,
doi:10.1021/ol006605hBeg, Shivangi, Meena, Structural Prediction and mutational analysis of Rv3906c gene of Mycobacterium tuberculosis H 37 Rv to determine its essentiality in survival, Adv Bioinform,
doi:10.1155/2018/6152014Ben-Zvi, Kivity, Langevitz, Shoenfeld, Hydroxychloroquine: from malaria to autoimmunity, Clin Rev Allergy Immunol
Biasini, Bienert, Waterhouse, Arnold, Studer et al., SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information, Nucleic Acids Res,
doi:10.1093/nar/gku340Cao, Xiao, Cao, Li, Kumaki et al., Inhibition of novel reassortant avian influenza H7N9 virus infection in vitro with three antiviral drugs, oseltamivir, peramivir and favipiravir, Antiviral Chem Chemother,
doi:10.3851/IMP2672Chaccour, Hammann, Ramón-García, Rabinovich, Ivermectin and Novel Coronavirus Disease (COVID-19): Keeping Rigor in Times of Urgency, Am J Trop Med Hygiene,
doi:10.4269/ajtmh.20-0271Chen, Yiu, Wong, Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates, F1000Research,
doi:10.12688/f1000research.22457.1Cheng, Zhang, Xie, Jiang, Arnold et al., Expression, purification, and characterization of SARS coronavirus RNA polymerase, Virology,
doi:10.1016/j.virol.2005.02.017Erion, Bullough, Lin, Hong, HepDirect prodrugs for targeting nucleotide-based antiviral drugs to the liver, Curr Opin Investig Drugs
Fantini, Scala, Chahinian, Yahi, Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105960Flierl, Nero, Lim, Arthur, Yao et al., Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators, J Exp Med,
doi:10.1084/jem.20140391Fox, Dixon, Guarrasi, Krubel, Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study, Lupus
Fu, Li, Zhang, Strong orbital Interaction in pi-pi Stacking System
Gao, Gao, Yan, Huang, Liu et al., Structure of the RNA-dependent RNA polymerase from COVID-19 virus, Science
Gao, Tian, Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends,
doi:10.5582/bst.2020.01047Hasan, Hossain, Analysis of COVID-19 M protein for possible clues regarding virion stability , longevity and spreading,
doi:10.31219/osf.io/e7jkcHenderleiter, Smart, Anderson, Elian, How do organic chemistry students understand and apply hydrogen bonding?, J Chem Educ,
doi:10.1021/ed078p1126Huang, Bosch, Li, Li, Kyoung et al., SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells, J Biol Chem,
doi:10.1074/jbc.M508381200Jeffrey, An introduction to hydrogen bonding
Khan, Zia, Ashraf, Uddin, Ul-Haq, Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach, J Biomol Struct Dyn,
doi:10.1080/07391102.2020.1751298Lee, Yang, Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys Rev B,
doi:10.1103/PhysRevB.37.785Li, Moore, Vasilieva, Sui, Wong et al., Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus, Nature,
doi:10.1038/nature02145Lüthy, Bowie, Eisenberg, Assessment of protein models with three-dimensional profiles, Nature,
doi:10.1038/356083a0Pamidighantam, Nakandala, Abeysinghe, Wimalasena, Yodage et al., Community science exemplars in SEAGrid science gateway: apache airavata based implementation of advanced infrastructure, Proc Comput Sci,
doi:10.1016/j.procs.2016.05.535Pettersen, Goddard, Huang, Couch, Greenblatt et al., UCSF Chimera-a visualization system for exploratory research and analysis, J Comput Chem
Prabakaran, Xiao, Dimitrov, A model of the ACE2 structure and function as a SARS-CoV receptor, Biochem Biophys Res Commun,
doi:10.1016/j.bbrc.2003.12.081Shi, Sivaraman, Song, Mechanism for controlling the dimermonomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3C-like protease, J Virol,
doi:10.1128/JVI.02680-07Solowiej, Thomson, Ryan, Luo, He et al., Steady-State and pre-steady-state kinetic evaluation of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro Cysteine protease: development of an ion-pair model for catalysis, Biochemistry,
doi:10.1021/bi702107vTrott, Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J Comput Chem,
doi:10.1002/jcc.21334Van Doremalen, Bushmaker, Morris, Holbrook, Gamble et al., Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1, N Engl J Med,
doi:10.1056/NEJMc2004973Walls, Park, Tortorici, Wall, Mcguire et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Cell,
doi:10.1016/j.cell.2020.02.058Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0Wang, Lai, Wang, Further development and validation of empirical scoring functions for structure-based binding affinity 22 Page 12 of 12 prediction, J Comput Aided Mol Des,
doi:10.1023/A:1016357811882Wang, Wang, Chen, Qin, Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures, J Med Virol,
doi:10.1002/jmv.25748Waterhouse, Bertoni, Bienert, Studer, Tauriello et al., SWISS-MODEL: homology modelling of protein structures and complexes, Nucleic Acids Res,
doi:10.1093/nar/gky427Williams, Headd, Moriarty, Prisant, Videau et al., MolProbity: More and better reference data for improved all-atom structure validation, Protein Sci,
doi:10.1002/pro.3330Yang, Roy, Zhang, Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment, Bioinformatics,
doi:10.1093/bioinformatics/btt447Yang, Yang, Ding, Liu, Lou et al., The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor, Proc Natl Acad Sci
{ 'indexed': {'date-parts': [[2023, 6, 27]], 'date-time': '2023-06-27T19:12:35Z', 'timestamp': 1687893155569},
'reference-count': 61,
'publisher': 'Springer Science and Business Media LLC',
'issue': '1',
'license': [ { 'start': { 'date-parts': [[2021, 3, 25]],
'date-time': '2021-03-25T00:00:00Z',
'timestamp': 1616630400000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.springer.com/tdm'},
{ 'start': { 'date-parts': [[2021, 3, 25]],
'date-time': '2021-03-25T00:00:00Z',
'timestamp': 1616630400000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://www.springer.com/tdm'}],
'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 12]]},
'DOI': '10.1007/s13721-021-00299-2',
'type': 'journal-article',
'created': {'date-parts': [[2021, 3, 25]], 'date-time': '2021-03-25T21:59:06Z', 'timestamp': 1616709546000},
'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy',
'source': 'Crossref',
'is-referenced-by-count': 5,
'title': 'In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent '
'RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV',
'prefix': '10.1007',
'volume': '10',
'author': [ {'given': 'Inemesit A.', 'family': 'Udofia', 'sequence': 'first', 'affiliation': []},
{'given': 'Kofoworola O.', 'family': 'Gbayo', 'sequence': 'additional', 'affiliation': []},
{'given': 'Oluwakemi A.', 'family': 'Oloba-Whenu', 'sequence': 'additional', 'affiliation': []},
{'given': 'Taofeek B.', 'family': 'Ogunbayo', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-6633-6066',
'authenticated-orcid': False,
'given': 'Chukwuemeka',
'family': 'Isanbor',
'sequence': 'additional',
'affiliation': []}],
'member': '297',
'published-online': {'date-parts': [[2021, 3, 25]]},
'reference': [ { 'issue': '1',
'key': '299_CR1',
'doi-asserted-by': 'publisher',
'first-page': '44',
'DOI': '10.1038/s41591-020-0820-9',
'volume': '89',
'author': 'KG Andersen',
'year': '2020',
'unstructured': 'Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (2020) The '
'proximal origin of SARS-CoV-2. Nat Med 89(1):44–48. '
'https://doi.org/10.1038/s41591-020-0820-9',
'journal-title': 'Nat Med'},
{ 'issue': '24',
'key': '299_CR2',
'doi-asserted-by': 'publisher',
'first-page': '3865',
'DOI': '10.1021/ol006605h',
'volume': '2',
'author': 'AC Bajji',
'year': '2000',
'unstructured': 'Bajji AC, Davis DR (2000) Synthesis and biophysical characterization of '
'tRNALys,3 anticodon stem-loop RNAs containing the mcm5s2U nucleoside. '
'Org Lett 2(24):3865–3868. https://doi.org/10.1021/ol006605h',
'journal-title': 'Org Lett'},
{ 'key': '299_CR3',
'doi-asserted-by': 'publisher',
'DOI': '10.1155/2018/6152014',
'author': 'MA Beg',
'year': '2018',
'unstructured': 'Beg MA, Shivangi TSC, Meena LS (2018) Structural Prediction and '
'mutational analysis of Rv3906c gene of Mycobacterium tuberculosis H37Rv '
'to determine its essentiality in survival. Adv Bioinform. '
'https://doi.org/10.1155/2018/6152014',
'journal-title': 'Adv Bioinform'},
{ 'issue': '2',
'key': '299_CR01',
'doi-asserted-by': 'publisher',
'first-page': '145',
'DOI': '10.1007/s12016-010-8243-x',
'volume': '42',
'author': 'I Ben-Zvi',
'year': '2012',
'unstructured': 'Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y (2012) Hydroxychloroquine: '
'from malaria to autoimmunity. Clin Rev Allergy Immunol 42(2):145–153',
'journal-title': 'Clin Rev Allergy Immunol'},
{ 'issue': 'W1',
'key': '299_CR4',
'doi-asserted-by': 'publisher',
'first-page': 'W252',
'DOI': '10.1093/nar/gku340',
'volume': '42',
'author': 'M Biasini',
'year': '2014',
'unstructured': 'Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, '
'Kiefer F, Cassarino TG, Bertoni M, Bordoli L, Schwede T (2014) '
'SWISS-MODEL: modelling protein tertiary and quaternary structure using '
'evolutionary information. Nucleic Acids Res 42(W1):W252–W258. '
'https://doi.org/10.1093/nar/gku340',
'journal-title': 'Nucleic Acids Res'},
{ 'key': '299_CR5',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.antiviral.2020.104787',
'author': 'L Caly',
'year': '2020',
'unstructured': 'Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (2020) The '
'FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in '
'vitro. Antivir Res. https://doi.org/10.1016/j.antiviral.2020.104787',
'journal-title': 'Antivir Res'},
{ 'issue': '6',
'key': '299_CR6',
'doi-asserted-by': 'publisher',
'first-page': '237',
'DOI': '10.3851/IMP2672',
'volume': '23',
'author': 'R-Y Cao',
'year': '2014',
'unstructured': 'Cao R-Y, Xiao J-H, Cao B, Li S, Kumaki Y, Zhong W (2014) Inhibition of '
'novel reassortant avian influenza H7N9 virus infection in vitro with '
'three antiviral drugs, oseltamivir, peramivir and favipiravir. Antiviral '
'Chem Chemother 23(6):237–240. https://doi.org/10.3851/IMP2672',
'journal-title': 'Antiviral Chem Chemother'},
{ 'key': '299_CR7',
'doi-asserted-by': 'publisher',
'DOI': '10.4269/ajtmh.20-0271',
'author': 'C Chaccour',
'year': '2020',
'unstructured': 'Chaccour C, Hammann F, Ramón-García S, Rabinovich NR (2020) Ivermectin '
'and Novel Coronavirus Disease (COVID-19): Keeping Rigor in Times of '
'Urgency. Am J Trop Med Hygiene. https://doi.org/10.4269/ajtmh.20-0271',
'journal-title': 'Am J Trop Med Hygiene'},
{ 'issue': 'Suppl 2',
'key': '299_CR8',
'doi-asserted-by': 'publisher',
'first-page': 'S118',
'DOI': '10.3978/j.issn.2072-1439.2013.06.19',
'volume': '5 Suppl 2',
'author': 'PKS Chan',
'year': '2013',
'unstructured': 'Chan PKS, Chan MCW (2013) Tracing the SARS-coronavirus. J Thorac Dis 5 '
'Suppl 2(Suppl 2):S118–S121. '
'https://doi.org/10.3978/j.issn.2072-1439.2013.06.19',
'journal-title': 'J Thorac Dis'},
{ 'key': '299_CR9',
'doi-asserted-by': 'publisher',
'first-page': '129',
'DOI': '10.12688/f1000research.22457.1',
'volume': '9',
'author': 'YW Chen',
'year': '2020',
'unstructured': 'Chen YW, Yiu C-PB, Wong K-Y (2020) Prediction of the SARS-CoV-2 '
'(2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening '
'reveals velpatasvir, ledipasvir, and other drug repurposing candidates. '
'F1000Research 9:129. https://doi.org/10.12688/f1000research.22457.1',
'journal-title': 'F1000Research'},
{ 'issue': '2',
'key': '299_CR10',
'doi-asserted-by': 'publisher',
'first-page': '165',
'DOI': '10.1016/j.virol.2005.02.017',
'volume': '335',
'author': 'A Cheng',
'year': '2005',
'unstructured': 'Cheng A, Zhang W, Xie Y, Jiang W, Arnold E, Sarafianos SG, Ding J (2005) '
'Expression, purification, and characterization of SARS coronavirus RNA '
'polymerase. Virology 335(2):165–176. '
'https://doi.org/10.1016/j.virol.2005.02.017',
'journal-title': 'Virology'},
{ 'key': '299_CR11',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.ijantimicag.2020.105932',
'author': 'P Colson',
'year': '2020',
'unstructured': 'Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D (2020) Chloroquine '
'and hydroxychloroquine as available weapons to fight COVID-19. Int J '
'Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2020.105932',
'journal-title': 'Int J Antimicrob Agents'},
{ 'key': '299_CR12',
'doi-asserted-by': 'publisher',
'unstructured': 'Corman VM, Muth D, Niemeyer D, Drosten C (2018) Hosts and sources of '
'endemic human coronaviruses. In: Advances in virus research, vol. 100. '
'Elsevier Inc., pp 163–188. https://doi.org/10.1016/bs.aivir.2018.01.001',
'DOI': '10.1016/bs.aivir.2018.01.001'},
{ 'key': '299_CR13',
'doi-asserted-by': 'publisher',
'first-page': '243',
'DOI': '10.1007/978-1-4939-2269-7_19',
'volume-title': 'Chemical biology',
'author': 'S Dallakyan',
'year': '2015',
'unstructured': 'Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking '
'with PyRx BT—chemical biology: methods and protocols. In: Hempel JE, '
'Williams CH, Hong CC (eds) Chemical biology. Springer New York, pp '
'243–250. https://doi.org/10.1007/978-1-4939-2269-7_19'},
{ 'key': '299_CR14',
'unstructured': 'Erion MD, Bullough DA, Lin C-C, Hong Z (2006). HepDirect prodrugs for '
'targeting nucleotide-based antiviral drugs to the liver. Curr Opin '
'Investig Drugs (London, England\u202f: 2000) 7(2): 109–117. '
'http://europepmc.org/abstract/MED/16499280. Accessed 23 Apr 2020'},
{ 'key': '299_CR15',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.ijantimicag.2020.105960',
'author': 'J Fantini',
'year': '2020',
'unstructured': 'Fantini J, Di Scala C, Chahinian H, Yahi N (2020) Structural and '
'molecular modelling studies reveal a new mechanism of action of '
'chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J '
'Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2020.105960',
'journal-title': 'Int J Antimicrob Agents'},
{ 'issue': '2',
'key': '299_CR16',
'doi-asserted-by': 'publisher',
'first-page': '129',
'DOI': '10.1084/jem.20140391',
'volume': '212',
'author': 'U Flierl',
'year': '2015',
'unstructured': 'Flierl U, Nero TL, Lim B, Arthur JF, Yao Y, Jung SM, Gitz E, Pollitt AY, '
'Zaldivia MTK, Jandrot-Perrus M, Schäfer A, Nieswandt B, Andrews RK, '
'Parker MW, Gardiner EE, Peter K (2015) Phosphorothioate backbone '
'modifications of nucleotide-based drugs are potent platelet activators. '
'J Exp Med 212(2):129–137. https://doi.org/10.1084/jem.20140391',
'journal-title': 'J Exp Med'},
{ 'issue': '1_suppl',
'key': '299_CR02',
'doi-asserted-by': 'publisher',
'first-page': '31',
'DOI': '10.1177/0961203396005001081',
'volume': '5',
'author': 'RI Fox',
'year': '1996',
'unstructured': 'Fox RI, Dixon R, Guarrasi V, Krubel S (1996) Treatment of primary '
"Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label "
'study. Lupus 5(1_suppl):31–36',
'journal-title': 'Lupus'},
{ 'key': '299_CR17',
'unstructured': 'Fu X-X, Li J-F, Zhang R-Q (2016) Strong orbital Interaction in pi-pi '
'Stacking System. In: arXiv e-prints arXiv:1601.01150. '
'https://ui.adsabs.harvard.edu/abs/2016arXiv160101150F. Accessed 23 Apr '
'2020'},
{ 'issue': '1',
'key': '299_CR18',
'doi-asserted-by': 'publisher',
'first-page': '72',
'DOI': '10.5582/bst.2020.01047',
'volume': '14',
'author': 'J Gao',
'year': '2020',
'unstructured': 'Gao J, Tian Z, Yang X (2020a) Breakthrough: Chloroquine phosphate has '
'shown apparent efficacy in treatment of COVID-19 associated pneumonia in '
'clinical studies. Biosci Trends 14(1):72–73. '
'https://doi.org/10.5582/bst.2020.01047',
'journal-title': 'Biosci Trends'},
{ 'issue': '6492',
'key': '299_CR19',
'doi-asserted-by': 'publisher',
'first-page': '779',
'DOI': '10.1126/science.abb7498',
'volume': '368',
'author': 'Y Gao',
'year': '2020',
'unstructured': 'Gao Y, 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, Wang Q, Lou Z, '
'Rao Z (2020b) Structure of the RNA-dependent RNA polymerase from '
'COVID-19 virus. Science 368(6492):779–782',
'journal-title': 'Science'},
{ 'key': '299_CR20',
'doi-asserted-by': 'publisher',
'unstructured': 'Hasan S, Hossain MM (2020) Analysis of COVID-19 M protein for possible '
'clues regarding virion stability , longevity and spreading. '
'https://doi.org/10.31219/osf.io/e7jkc',
'DOI': '10.31219/osf.io/e7jkc'},
{ 'issue': '8',
'key': '299_CR21',
'doi-asserted-by': 'publisher',
'first-page': '1126',
'DOI': '10.1021/ed078p1126',
'volume': '78',
'author': 'J Henderleiter',
'year': '2001',
'unstructured': 'Henderleiter J, Smart R, Anderson J, Elian O (2001) How do organic '
'chemistry students understand and apply hydrogen bonding? J Chem Educ '
'78(8):1126. https://doi.org/10.1021/ed078p1126',
'journal-title': 'J Chem Educ'},
{ 'issue': '6',
'key': '299_CR22',
'doi-asserted-by': 'publisher',
'first-page': '3198',
'DOI': '10.1074/jbc.M508381200',
'volume': '281',
'author': 'IC Huang',
'year': '2006',
'unstructured': 'Huang IC, Bosch BJ, Li F, Li W, Kyoung HL, Ghiran S, Vasilieva N, '
'Dermody TS, Harrison SC, Dormitzer PR, Farzan M, Rottier PJM, Choe H '
'(2006) SARS coronavirus, but not human coronavirus NL63, utilizes '
'cathepsin L to infect ACE2-expressing cells. J Biol Chem '
'281(6):3198–3203. https://doi.org/10.1074/jbc.M508381200',
'journal-title': 'J Biol Chem'},
{ 'key': '299_CR23',
'unstructured': 'Jeffrey GA (1997) An introduction to hydrogen bonding (12th ed.). Oxford '
'University Press. https://books.google.fr/books?id=ZRAFifo37QsC. '
'Accessed 23 Apr 2020'},
{ 'issue': '7811',
'key': '299_CR24',
'doi-asserted-by': 'publisher',
'first-page': '289',
'DOI': '10.1038/s41586-020-2223-y',
'volume': '582',
'author': 'Z Jin',
'year': '2020',
'unstructured': 'Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng '
'C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, '
'Yang H (2020) Structure of Mpro from SARS-CoV-2 and discovery of its '
'inhibitors. Nature 582(7811):289–293. '
'https://doi.org/10.1038/s41586-020-2223-y',
'journal-title': 'Nature'},
{ 'key': '299_CR25',
'doi-asserted-by': 'publisher',
'DOI': '10.1101/2020.01.30.927574',
'author': 'J Ju',
'year': '2020',
'unstructured': 'Ju J, Kumar S, Li X, Jockusch S, Russo JJ (2020a) Nucleotide analogues '
'as inhibitors of viral polymerases. BioRxiv. '
'https://doi.org/10.1101/2020.01.30.927574',
'journal-title': 'BioRxiv'},
{ 'key': '299_CR26',
'doi-asserted-by': 'publisher',
'DOI': '10.1101/2020.03.12.989186',
'author': 'J Ju',
'year': '2020',
'unstructured': 'Ju J, Li X, Kumar S, Jockusch S, Chien M, Tao C, Morozova I, Kalachikov '
'S, Kirchdoerfer RN, Russo JJ (2020b) Nucleotide Analogues as Inhibitors '
'of SARS-CoV Polymerase. BioRxiv. '
'https://doi.org/10.1101/2020.03.12.989186',
'journal-title': 'BioRxiv'},
{ 'issue': '1',
'key': '299_CR27',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1080/07391102.2020.1751298',
'volume': '9',
'author': 'SA Khan',
'year': '2020',
'unstructured': 'Khan SA, Zia K, Ashraf S, Uddin R, Ul-Haq Z (2020) Identification of '
'chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated '
'computational approach. J Biomol Struct Dyn 9(1):1–10. '
'https://doi.org/10.1080/07391102.2020.1751298',
'journal-title': 'J Biomol Struct Dyn'},
{ 'issue': '1',
'key': '299_CR28',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1038/s41467-019-10280-3',
'volume': '10',
'author': 'RN Kirchdoerfer',
'year': '2019',
'unstructured': 'Kirchdoerfer RN, Ward AB (2019) Structure of the SARS-CoV nsp12 '
'polymerase bound to nsp7 and nsp8 co-factors. Nat Commun 10(1):1–9. '
'https://doi.org/10.1038/s41467-019-10280-3',
'journal-title': 'Nat Commun'},
{ 'issue': '2',
'key': '299_CR29',
'doi-asserted-by': 'publisher',
'first-page': '785',
'DOI': '10.1103/PhysRevB.37.785',
'volume': '37',
'author': 'C Lee',
'year': '1988',
'unstructured': 'Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti '
'correlation-energy formula into a functional of the electron density. '
'Phys Rev B 37(2):785–789. https://doi.org/10.1103/PhysRevB.37.785',
'journal-title': 'Phys Rev B'},
{ 'issue': '3',
'key': '299_CR30',
'doi-asserted-by': 'publisher',
'first-page': '149',
'DOI': '10.1038/d41573-020-00016-0',
'volume': '19',
'author': 'G Li',
'year': '2020',
'unstructured': 'Li G, De Clercq E (2020) Therapeutic options for the 2019 novel '
'coronavirus (2019-nCoV). Nat Rev Drug Discov 19(3):149–150. '
'https://doi.org/10.1038/d41573-020-00016-0',
'journal-title': 'Nat Rev Drug Discov'},
{ 'issue': '6965',
'key': '299_CR31',
'doi-asserted-by': 'publisher',
'first-page': '450',
'DOI': '10.1038/nature02145',
'volume': '426',
'author': 'W Li',
'year': '2003',
'unstructured': 'Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, '
'Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) '
'Angiotensin-converting enzyme 2 is a functional receptor for the SARS '
'coronavirus. Nature 426(6965):450–454. '
'https://doi.org/10.1038/nature02145',
'journal-title': 'Nature'},
{ 'issue': '6364',
'key': '299_CR32',
'doi-asserted-by': 'publisher',
'first-page': '83',
'DOI': '10.1038/356083a0',
'volume': '356',
'author': 'R Lüthy',
'year': '1992',
'unstructured': 'Lüthy R, Bowie JU, Eisenberg D (1992) Assessment of protein models with '
'three-dimensional profiles. Nature 356(6364):83–85. '
'https://doi.org/10.1038/356083a0',
'journal-title': 'Nature'},
{ 'key': '299_CR33',
'doi-asserted-by': 'publisher',
'first-page': '48',
'DOI': '10.1016/j.antiviral.2017.02.004',
'volume': '141',
'author': 'B Martin',
'year': '2017',
'unstructured': 'Martin B, Canard B, Decroly E (2017) Filovirus proteins for antiviral '
'drug discovery: Structure/function bases of the replication cycle. '
'Antivir Res 141:48–61. https://doi.org/10.1016/j.antiviral.2017.02.004',
'journal-title': 'Antivir Res'},
{ 'issue': '7',
'key': '299_CR34',
'doi-asserted-by': 'publisher',
'first-page': '2191',
'DOI': '10.1039/C2SC20045G',
'volume': '3',
'author': 'CR Martinez',
'year': '2012',
'unstructured': 'Martinez CR, Iverson BL (2012) Rethinking the term “pi-stacking.” Chem '
'Sci 3(7):2191–2201. https://doi.org/10.1039/C2SC20045G',
'journal-title': 'Chem Sci'},
{ 'issue': '06',
'key': '299_CR35',
'doi-asserted-by': 'publisher',
'first-page': '193',
'DOI': '10.1016/S0065-3527(06)66005-3',
'volume': '65',
'author': 'PS Masters',
'year': '2006',
'unstructured': 'Masters PS (2006) The molecular biology of coronaviruses. Adv Virus Res '
'65(06):193–292. https://doi.org/10.1016/S0065-3527(06)66005-3',
'journal-title': 'Adv Virus Res'},
{ 'key': '299_CR36',
'doi-asserted-by': 'publisher',
'first-page': '1927',
'DOI': '10.1016/j.procs.2016.05.535',
'volume': '80',
'author': 'S Pamidighantam',
'year': '2016',
'unstructured': 'Pamidighantam S, Nakandala S, Abeysinghe E, Wimalasena C, Yodage SR, '
'Marru S, Pierce M (2016) Community science exemplars in SEAGrid science '
'gateway: apache airavata based implementation of advanced '
'infrastructure. Proc Comput Sci 80:1927–1939. '
'https://doi.org/10.1016/j.procs.2016.05.535',
'journal-title': 'Proc Comput Sci'},
{ 'issue': '4',
'key': '299_CR37',
'doi-asserted-by': 'publisher',
'first-page': '617',
'DOI': '10.1007/s00726-007-0015-4',
'volume': '34',
'author': 'SK Panigrahi',
'year': '2008',
'unstructured': 'Panigrahi SK (2008) Strong and weak hydrogen bonds in protein-ligand '
'complexes of kinases: a comparative study. Amino Acids 34(4):617–633. '
'https://doi.org/10.1007/s00726-007-0015-4',
'journal-title': 'Amino Acids'},
{ 'key': '299_CR38',
'doi-asserted-by': 'publisher',
'first-page': '387',
'DOI': '10.1016/B978-0-12-815422-9.00014-0',
'volume-title': 'Viral polymerases',
'author': 'VM Patil',
'year': '2019',
'unstructured': 'Patil VM, Balasubramanian K, Masand N (2019) Chapter 14—dengue virus '
'polymerase: a crucial target for antiviral drug discovery. In: Gupta '
'SPBT-VP (ed) Viral polymerases. Academic Press, pp 387–428. '
'https://doi.org/10.1016/B978-0-12-815422-9.00014-0'},
{ 'key': '299_CR39',
'doi-asserted-by': 'publisher',
'first-page': '307',
'DOI': '10.1385/0-89603-246-9:307',
'volume-title': 'Computer analysis of sequence data',
'author': 'WR Pearson',
'year': '1994',
'unstructured': 'Pearson WR (1994) Using the FASTA program to search protein and DNA '
'sequence databases. In: Griffin AM, Griffin HG (eds) Computer analysis '
'of sequence data. Humana Press, pp 307–331. '
'https://doi.org/10.1385/0-89603-246-9:307'},
{ 'key': '299_CR40',
'doi-asserted-by': 'publisher',
'first-page': '1605',
'DOI': '10.1002/jcc.20084',
'volume': '25',
'author': 'EF Pettersen',
'year': '2004',
'unstructured': 'Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, '
'Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory '
'research and analysis. J Comput Chem 25:1605',
'journal-title': 'J Comput Chem'},
{ 'issue': '1',
'key': '299_CR41',
'doi-asserted-by': 'publisher',
'first-page': '235',
'DOI': '10.1016/j.bbrc.2003.12.081',
'volume': '314',
'author': 'P Prabakaran',
'year': '2004',
'unstructured': 'Prabakaran P, Xiao X, Dimitrov DS (2004) A model of the ACE2 structure '
'and function as a SARS-CoV receptor. Biochem Biophys Res Commun '
'314(1):235–241. https://doi.org/10.1016/j.bbrc.2003.12.081',
'journal-title': 'Biochem Biophys Res Commun'},
{ 'key': '299_CR42',
'doi-asserted-by': 'publisher',
'unstructured': 'Raha K, Merz KMBT-ARC C (2005) Chapter 9 Calculating binding free energy '
'in protein–ligand interaction. In: Annual reports in computational '
'chemistry, vol. 1. Elsevier, pp. 113–130. '
'https://doi.org/10.1016/S1574-1400(05)01009-1',
'DOI': '10.1016/S1574-1400(05)01009-1'},
{ 'issue': '9',
'key': '299_CR43',
'doi-asserted-by': 'publisher',
'first-page': '4620LP',
'DOI': '10.1128/JVI.02680-07',
'volume': '82',
'author': 'J Shi',
'year': '2008',
'unstructured': 'Shi J, Sivaraman J, Song J (2008) Mechanism for controlling the '
'dimer-monomer switch and coupling dimerization to catalysis of the '
'severe acute respiratory syndrome coronavirus 3C-like protease. J Virol '
'82(9):4620LP – 4629. https://doi.org/10.1128/JVI.02680-07',
'journal-title': 'J Virol'},
{ 'issue': '8',
'key': '299_CR44',
'doi-asserted-by': 'publisher',
'first-page': '2617',
'DOI': '10.1021/bi702107v',
'volume': '47',
'author': 'J Solowiej',
'year': '2008',
'unstructured': 'Solowiej J, Thomson JA, Ryan K, Luo C, He M, Lou J, Murray BW (2008) '
'Steady-State and pre-steady-state kinetic evaluation of severe acute '
'respiratory syndrome coronavirus (SARS-CoV) 3CLpro Cysteine protease: '
'development of an ion-pair model for catalysis. Biochemistry '
'47(8):2617–2630. https://doi.org/10.1021/bi702107v',
'journal-title': 'Biochemistry'},
{ 'issue': '12',
'key': '299_CR45',
'doi-asserted-by': 'publisher',
'first-page': '2939',
'DOI': '10.1099/0022-1317-69-12-2939',
'volume': '69',
'author': 'W Spaan',
'year': '1988',
'unstructured': 'Spaan W, Cavanagh D, Horzinek MC (1988) Coronaviruses: structure and '
'genome expression. J Gen Virol 69(12):2939–2952. '
'https://doi.org/10.1099/0022-1317-69-12-2939',
'journal-title': 'J Gen Virol'},
{ 'key': '299_CR46',
'doi-asserted-by': 'publisher',
'DOI': '10.3390/molecules22071038',
'author': 'V Spiwok',
'year': '2017',
'unstructured': 'Spiwok V (2017) CH/π Interactions in Carbohydrate Recognition. '
'Molecules. https://doi.org/10.3390/molecules22071038',
'journal-title': 'Molecules'},
{ 'key': '299_CR47',
'doi-asserted-by': 'publisher',
'first-page': '69',
'DOI': '10.1016/B978-0-12-815422-9.00003-6',
'volume-title': 'Viral polymerases',
'author': 'S Tomar',
'year': '2019',
'unstructured': 'Tomar S, Mudgal R, Pareek A (2019) Chapter 3—RNA-dependent RNA '
'polymerase of alphaviruses: a potential target for the design of drugs '
'against alphaviruses. In: Gupta SPBT-VP (ed) Viral polymerases. Academic '
'Press, pp 69–94. https://doi.org/10.1016/B978-0-12-815422-9.00003-6'},
{ 'key': '299_CR48',
'doi-asserted-by': 'publisher',
'first-page': '104762',
'DOI': '10.1016/j.antiviral.2020.104762',
'volume': '177',
'author': 'F Touret',
'year': '2020',
'unstructured': 'Touret F, de Lamballerie X (2020) Of chloroquine and COVID-19. Antivir '
'Res 177:104762. https://doi.org/10.1016/j.antiviral.2020.104762',
'journal-title': 'Antivir Res'},
{ 'issue': '2',
'key': '299_CR49',
'doi-asserted-by': 'publisher',
'first-page': '455',
'DOI': '10.1002/jcc.21334',
'volume': '31',
'author': 'O Trott',
'year': '2010',
'unstructured': 'Trott O, Olson AJ (2010) AutoDock Vina: Improving the speed and accuracy '
'of docking with a new scoring function, efficient optimization, and '
'multithreading. J Comput Chem 31(2):455–461. '
'https://doi.org/10.1002/jcc.21334',
'journal-title': 'J Comput Chem'},
{ 'issue': '16',
'key': '299_CR50',
'doi-asserted-by': 'publisher',
'first-page': '1564',
'DOI': '10.1056/NEJMc2004973',
'volume': '382',
'author': 'N van Doremalen',
'year': '2020',
'unstructured': 'van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, '
'Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, '
'Lloyd-Smith JO, de Wit E, Munster VJ (2020) Aerosol and surface '
'stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med '
'382(16):1564–1567. https://doi.org/10.1056/NEJMc2004973',
'journal-title': 'N Engl J Med'},
{ 'key': '299_CR51',
'doi-asserted-by': 'publisher',
'first-page': '1',
'DOI': '10.1016/j.cell.2020.02.058',
'volume': '180',
'author': 'AC Walls',
'year': '2020',
'unstructured': 'Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) '
'Structure, function, and antigenicity of the SARS-CoV-2 spike '
'glycoprotein. Cell 180:1–12. https://doi.org/10.1016/j.cell.2020.02.058',
'journal-title': 'Cell'},
{ 'issue': '1',
'key': '299_CR53',
'doi-asserted-by': 'publisher',
'first-page': '11',
'DOI': '10.1023/A:1016357811882',
'volume': '16',
'author': 'R Wang',
'year': '2002',
'unstructured': 'Wang R, Lai L, Wang S (2002) Further development and validation of '
'empirical scoring functions for structure-based binding affinity '
'prediction. J Comput Aided Mol Des 16(1):11–26. '
'https://doi.org/10.1023/A:1016357811882',
'journal-title': 'J Comput Aided Mol Des'},
{ 'issue': '3',
'key': '299_CR52',
'doi-asserted-by': 'publisher',
'first-page': '269',
'DOI': '10.1038/s41422-020-0282-0',
'volume': '30',
'author': 'M Wang',
'year': '2020',
'unstructured': 'Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao '
'G (2020a) Remdesivir and chloroquine effectively inhibit the recently '
'emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3):269–271. '
'https://doi.org/10.1038/s41422-020-0282-0',
'journal-title': 'Cell Res'},
{ 'key': '299_CR54',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/jmv.25748',
'author': 'Y Wang',
'year': '2020',
'unstructured': 'Wang Y, Wang Y, Chen Y, Qin Q (2020b) Unique epidemiological and '
'clinical features of the emerging 2019 novel coronavirus pneumonia '
'(COVID-19) implicate special control measures. J Med Virol. '
'https://doi.org/10.1002/jmv.25748',
'journal-title': 'J Med Virol'},
{ 'issue': '1',
'key': '299_CR55',
'doi-asserted-by': 'publisher',
'first-page': '296',
'DOI': '10.1093/nar/gky427',
'volume': '46',
'author': 'A Waterhouse',
'year': '2018',
'unstructured': 'Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, '
'Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T (2018) '
'SWISS-MODEL: homology modelling of protein structures and complexes. '
'Nucleic Acids Res 46(1):296-W303. https://doi.org/10.1093/nar/gky427',
'journal-title': 'Nucleic Acids Res'},
{ 'key': '299_CR56',
'doi-asserted-by': 'publisher',
'unstructured': 'WHO (2020) Coronavirus disease (COVID-2019) situation reports 318. '
'https://doi.org/10.1093/nar/gkz966',
'DOI': '10.1093/nar/gkz966'},
{ 'issue': '1',
'key': '299_CR57',
'doi-asserted-by': 'publisher',
'first-page': '293',
'DOI': '10.1002/pro.3330',
'volume': '27',
'author': 'CJ Williams',
'year': '2018',
'unstructured': 'Williams CJ, Headd JJ, Moriarty NW, Prisant MG, Videau LL, Deis LN, '
'Verma V, Keedy DA, Hintze BJ, Chen VB, Jain S, Lewis SM, Arendall WB '
'III, Snoeyink J, Adams PD, Lovell SC, Richardson JS, Richardson DC '
'(2018) MolProbity: More and better reference data for improved all-atom '
'structure validation. Protein Sci 27(1):293–315. '
'https://doi.org/10.1002/pro.3330',
'journal-title': 'Protein Sci'},
{ 'issue': '23',
'key': '299_CR58',
'doi-asserted-by': 'publisher',
'first-page': '13190',
'DOI': '10.1073/pnas.1835675100',
'volume': '100',
'author': 'H Yang',
'year': '2003',
'unstructured': 'Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, Sun L, Mo L, Ye S, Pang H, '
'Gao GF, Anand K, Bartlam M, Hilgenfeld R, Rao Z (2003) The crystal '
'structures of severe acute respiratory syndrome virus main protease and '
'its complex with an inhibitor. Proc Natl Acad Sci USA '
'100(23):13190–13195',
'journal-title': 'Proc Natl Acad Sci USA'},
{ 'issue': '20',
'key': '299_CR59',
'doi-asserted-by': 'publisher',
'first-page': '2588',
'DOI': '10.1093/bioinformatics/btt447',
'volume': '29',
'author': 'J Yang',
'year': '2013',
'unstructured': 'Yang J, Roy A, Zhang Y (2013) Protein–ligand binding site recognition '
'using complementary binding-specific substructure comparison and '
'sequence profile alignment. Bioinformatics 29(20):2588–2595. '
'https://doi.org/10.1093/bioinformatics/btt447',
'journal-title': 'Bioinformatics'}],
'container-title': 'Network Modeling Analysis in Health Informatics and Bioinformatics',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s13721-021-00299-2.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/article/10.1007/s13721-021-00299-2/fulltext.html',
'content-type': 'text/html',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://link.springer.com/content/pdf/10.1007/s13721-021-00299-2.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 12, 9]],
'date-time': '2021-12-09T08:21:50Z',
'timestamp': 1639038110000},
'score': 1,
'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s13721-021-00299-2'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 3, 25]]},
'references-count': 61,
'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2021, 12]]}},
'alternative-id': ['299'],
'URL': 'http://dx.doi.org/10.1007/s13721-021-00299-2',
'relation': {},
'ISSN': ['2192-6662', '2192-6670'],
'subject': [],
'container-title-short': 'Netw Model Anal Health Inform Bioinforma',
'published': {'date-parts': [[2021, 3, 25]]},
'assertion': [ { 'value': '31 October 2020',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '25 January 2021',
'order': 2,
'name': 'revised',
'label': 'Revised',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '12 March 2021',
'order': 3,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '25 March 2021',
'order': 4,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': 'This content has been made available to all.',
'name': 'free',
'label': 'Free to read'}],
'article-number': '22'}
