{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:41:45Z","timestamp":1791999705692,"version":"4.4.0"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is one of the optimum targets for antiviral drug design and development. The hydroxyl groups of cytidine structures were modified with different aliphatic and aromatic groups to obtain 5\u1ffd-\n                    <jats:italic>O<\/jats:italic>\n                    -acyl and 2\u1ffd,3\u1ffd-di-\n                    <jats:italic>O<\/jats:italic>\n                    -acyl derivatives, and then, these derivatives were employed in molecular modeling, antiviral prediction, molecular docking, molecular dynamics, pharmacological and POM studies. Density functional theory (DFT) at the B3LYP\/6-31G++ level analyzed biochemical behavior and molecular electrostatic potential (MESP) of the modified cytidine derivatives. The antiviral parameters of the mutated derivatives revealed promising drug properties compared with those of standard antiviral drugs. Molecular docking has determined binding affinities and interactions between the cytidine derivatives and SARS-CoV-2 RdRp. The modified derivatives strongly interacted with prime Pro620 and Lys621 residues. The binding conformation and interactions stability were investigated by 200 ns of molecular dynamics simulations and predicted the compounds to firmly dock inside the RdRp binding pocket. Interestingly, the binding residues of the derivatives were revealed in high equilibrium showing an enhanced binding affinity for the molecules. Intermolecular interactions are dominated by both Van der Waals and electrostatic energies. Finally, the pharmacokinetic characterization of the optimized inhibitors confirmed the safety of derivatives due to their improved kinetic properties. The selected cytidine derivatives can be suggested as potential inhibitors against SARS-CoV-2. The POM Theory supports the hypothesis above by confirming the existence of an antiviral (O\n                    <jats:sup>\u03b4-<\/jats:sup>\n                    \u2014O\u2019\n                    <jats:sup>\u03b4-<\/jats:sup>\n                    ) pharmacophore site of Hits.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0273256","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T13:26:27Z","timestamp":1669641987000},"page":"e0273256","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":51,"title":["Potential SARS-CoV-2 RdRp inhibitors of cytidine derivatives: Molecular docking, molecular dynamic simulations, ADMET, and POM analyses for the identification of pharmacophore sites"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-9117","authenticated-orcid":true,"given":"Sarkar","family":"M. A. Kawsar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Hosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-6568","authenticated-orcid":true,"given":"Youness","family":"El Bakri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-6239","authenticated-orcid":true,"given":"Hamid","family":"Laaroussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taibi","family":"Ben Hadda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal A.","family":"Almalki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ozeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9333-7862","authenticated-orcid":true,"given":"Souraya","family":"Goumri-Said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"issue":"6504","key":"pone.0273256.ref001","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abb3231","article-title":"A short de novo synthesis of nucleoside analogs","volume":"369","author":"M Meanwell","year":"2020","journal-title":"Science"},{"issue":"9","key":"pone.0273256.ref002","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.3390\/molecules25092050","article-title":"Recent advances in the chemical synthesis and evaluation of anticancer nucleoside analogs","volume":"25","author":"M Guinan","year":"2020","journal-title":"Molecules"},{"issue":"6","key":"pone.0273256.ref003","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd4010","article-title":"Advances in the development of nucleoside and nucleotide analogs for cancer and viral diseases","volume":"12","author":"LP Jordheim","journal-title":"Nature Reviews Drug Discovery"},{"issue":"3","key":"pone.0273256.ref004","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jiph.2016.04.002","article-title":"BCX4430\u2013a broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease","volume":"9","author":"R Taylor","year":"2016","journal-title":"Journal of Infecttion and Public Health"},{"key":"pone.0273256.ref005","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1007\/s00044-017-1863-4","article-title":"Nucleoside analogs as potential antiviral agents for dengue virus infections","volume":"26","author":"KPV Pilay","year":"2017","journal-title":"Medicinal Chemistry Research"},{"issue":"5","key":"pone.0273256.ref006","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/infdis\/jiw226","article-title":"Nucleoside inhibitors of Zika virus","volume":"214","author":"L Eyer","year":"2016","journal-title":"The Journal Infectious Disease"},{"issue":"12","key":"pone.0273256.ref007","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1358\/dot.1998.34.12.487486","article-title":"Topical antiviral agents for herpes simplex virus infections","volume":"34","author":"R Hamuy","year":"1998","journal-title":"Drugs Today"},{"issue":"5","key":"pone.0273256.ref008","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1358\/dot.2003.39.5.740221","article-title":"Brivudine: a herpes virostatic with rapid antiviral activity and once-daily dosing","volume":"39","author":"X. Rabasseda","year":"2003","journal-title":"Drugs today"},{"issue":"6","key":"pone.0273256.ref009","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2165\/00003088-200847060-00001","article-title":"A review of the pharmacokinetics of abacavir.","volume":"47","author":"GJ Yuen","year":"2008","journal-title":"Clinical Pharmacokinetics"},{"issue":"6","key":"pone.0273256.ref010","first-page":"211","article-title":"Evaluation of the antimicrobial activity and cytotoxic effect of some uridine derivatives","volume":"12","author":"SMA Kawsar","year":"2018","journal-title":"International Journal of Biosciences"},{"issue":"4","key":"pone.0273256.ref011","doi-asserted-by":"crossref","first-page":"232","DOI":"10.4236\/ijoc.2015.54023","article-title":"Chemically modified uridine molecules incorporating acyl residues to enhance antibacterial and cytotoxic activities","volume":"5","author":"SMA Kawsar","year":"2015","journal-title":"International Journal Organic Chemistry"},{"key":"pone.0273256.ref012","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5267\/j.ccl.2015.12.001","article-title":"Simple and rapid synthesis of some nucleoside derivatives: structural and spectral characterization","volume":"5","author":"S Chowdhury","year":"2016","journal-title":"Current Chemistry Letters"},{"issue":"1","key":"pone.0273256.ref013","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2478\/auoc-2021-0002","article-title":"Synthesis, characterization, synergistic antimicrobial properties and molecular docking of sugar modified uridine derivatives","volume":"32","author":"J Maowa","year":"2021","journal-title":"Ovidius University Annals of Chemistry"},{"issue":"1","key":"pone.0273256.ref014","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3897\/pharmacia.68.e56543","article-title":"Synthesis of new series of pyrimidine nucleoside derivatives bearing the acyl moieties as potential antimicrobial agents","volume":"68","author":"MZH Bulbul","year":"2021","journal-title":"Pharmacia"},{"issue":"4","key":"pone.0273256.ref015","doi-asserted-by":"crossref","first-page":"7","DOI":"10.23893\/1307-2080.APS.05622","article-title":"An efficient approach to the synthesis of thymidine derivatives containing various acyl groups: characterization and antibacterial activities","volume":"56","author":"M Arifuzzaman","year":"2018","journal-title":"ACTA Pharmaceutica Sciencia"},{"issue":"2","key":"pone.0273256.ref016","doi-asserted-by":"crossref","first-page":"153","DOI":"10.15671\/hjbc.622038","article-title":"Novel methyl 4,6-O-benzylidene-\u03b1-D-glucopyranoside derivatives: Synthesis, structural characterization and evaluation of antibacterial activities","volume":"47","author":"M Islam","year":"2019","journal-title":"Hacettepe Journal of Biology and Chemistry"},{"issue":"4","key":"pone.0273256.ref017","first-page":"299","article-title":"Evaluation of MIC, MBC, MFC and anticancer activities of acylated methyl \u03b2-D-galactopyranoside esters","volume":"16","author":"MMH Misbah","year":"2020","journal-title":"International Journal of Biosciences"},{"key":"pone.0273256.ref018","first-page":"114","article-title":"Synthesis, antibacterial and cytotoxicity assessment of modified uridine molecules","volume":"6","author":"A Alam","year":"2021","journal-title":"Current Advances in Chemistry and Biochemistry"},{"issue":"2","key":"pone.0273256.ref019","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.4067\/S0717-97072021000205206","article-title":"Computational investigation of methyl \u03b1-D-glucopyranoside derivatives as inhibitor against bacteria, fungi and COVID-19 (SARS-2)","volume":"66","author":"S Kawsar","year":"2021","journal-title":"Journal of the Chilean Chemical Society"},{"issue":"1","key":"pone.0273256.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3797\/scipharm.1308-03","article-title":"Regioselective synthesis, characterization, and antimicrobial activities of some new monosaccharide derivatives.","volume":"82","author":"SMA Kawsar","year":"2014","journal-title":"Scientia Pharmaceutica"},{"issue":"2","key":"pone.0273256.ref021","doi-asserted-by":"crossref","first-page":"171","DOI":"10.17516\/1998-2836-0226","article-title":"Bromobenzoylation of methyl \u03b1-D-mannopyranoside: Synthesis and spectral characterization","volume":"14","author":"F Yasmina","year":"2021","journal-title":"Journal of Siberian Federal University Chemistry"},{"key":"pone.0273256.ref022","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1056\/NEJMoa066422","article-title":"Telbivudine versus lamivudine in patients with chronic hepatitis B","volume":"357","author":"LL Ching","year":"2007","journal-title":"The New England Journal Medicine"},{"issue":"4","key":"pone.0273256.ref023","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0278-5846(03)00086-1","article-title":"Dietary cytidine (5\u2032)-diphosphocholine supplementation protects against development of memory deficits in aging rats","volume":"27","author":"LA Teather","year":"2003","journal-title":"Progress Neuro-psychopharmacology and Biological Psychiatry"},{"issue":"4","key":"pone.0273256.ref024","doi-asserted-by":"crossref","first-page":"465","DOI":"10.17516\/1998-2836-0199","article-title":"Ribose moieties acylation and characterization of some cytidine analogs","volume":"13","author":"KM Rana","year":"2020","journal-title":"Journal of Siberian Federal University Chemistry"},{"issue":"2","key":"pone.0273256.ref025","doi-asserted-by":"crossref","first-page":"256","DOI":"10.29356\/jmcs.v65i2.1464","article-title":"Synthesis, characterization, and molecular docking against a receptor potein FimH of Escherichia coli (4XO8) of thymidine derivatives","volume":"65","author":"A Alam","year":"2021","journal-title":"Journal of the Mexican Chemical Society"},{"issue":"1","key":"pone.0273256.ref026","doi-asserted-by":"crossref","first-page":"47","DOI":"10.23893\/1307-2080.APS.05704","article-title":"Microbial efficacy and two step synthesis of uridine derivatives with spectral characterization","volume":"57","author":"SR Devi","year":"2019","journal-title":"ACTA Pharmaceutica Sciencia"},{"issue":"2","key":"pone.0273256.ref027","doi-asserted-by":"crossref","first-page":"59","DOI":"10.33435\/tcandtc.718807","article-title":"An optimization and pharmacokinetic studies of some thymidine derivatives","volume":"4","author":"SMA Kawsar","year":"2020","journal-title":"Turkish Computational and Theoretical Chemistry"},{"issue":"1\u20132","key":"pone.0273256.ref028","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF02991580","article-title":"Effect of cytidine analogs on cell growth and differentiation on a human neuroblastoma line","volume":"15","author":"S Bartolucci","year":"1989","journal-title":"Journal of Celluar Biophysics"},{"issue":"1","key":"pone.0273256.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2005.03.004","article-title":"KP-1212\/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis","volume":"67","author":"KS Harris","year":"2005","journal-title":"Antiviral Research"},{"issue":"1","key":"pone.0273256.ref030","doi-asserted-by":"crossref","first-page":"64","DOI":"10.5582\/bst.2020.01030","article-title":"Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment","volume":"14","author":"Z Wang","journal-title":"Bioscience Trends. 2020"},{"issue":"3","key":"pone.0273256.ref031","first-page":"385","article-title":"Pharmacokinetics and molecular docking studies of uridine derivatives as SARS-COV-2 Mpro inhibitors","volume":"9","author":"J Maowa","year":"2021","journal-title":"Physical Chemistry Research"},{"issue":"1","key":"pone.0273256.ref032","first-page":"88","article-title":"DFT study, physicochemical, molecular docking, and ADMET predictions of some modified uridine derivatives","volume":"8","author":"M Bulbul","year":"2021","journal-title":"International Journal of New Chemistry"},{"key":"pone.0273256.ref033","first-page":"613","article-title":"Interactions mechanism of commonly used drugs for the treatment of Covid-19","volume":"34","author":"C Sefa","year":"2020","journal-title":"Bulletin of the Chemical Society of Ethiopia"},{"key":"pone.0273256.ref034","doi-asserted-by":"crossref","first-page":"106012","DOI":"10.1016\/j.ijantimicag.2020.106012","article-title":"Computational screening of antagonists against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking","volume":"56","author":"Y Ran","year":"2020","journal-title":"International Journal of Antimicrobial Agents"},{"key":"pone.0273256.ref035","doi-asserted-by":"crossref","first-page":"100345","DOI":"10.1016\/j.imu.2020.100345","article-title":"Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study","volume":"19","author":"KP Abraham","year":"2020","journal-title":"Information medicine unlocked"},{"key":"pone.0273256.ref036","first-page":"3347","article-title":"An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study","volume":"39","author":"D Sourav","year":"2021","journal-title":"Journal of Biomolecular Structure Dynamics"},{"key":"pone.0273256.ref037","doi-asserted-by":"crossref","first-page":"132693","DOI":"10.1016\/j.molstruc.2022.132693","article-title":"Vibrational spectroscopic characterization and structural investigations of cepharanthine, a natural alkaloid","volume":"1258","author":"C Sefa","year":"2022","journal-title":"Journal of Molecular Structure"},{"key":"pone.0273256.ref038","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nature05819","article-title":"Synthesis and medical applications of oligosaccharides","volume":"446","author":"P. Seeberger","year":"2007","journal-title":"Nature"},{"key":"pone.0273256.ref039","article-title":"Gaussian 09, Revision d. 01, Gaussian","volume":"201","author":"M Frisch","year":"2009","journal-title":"Inc, Wallingford CT"},{"issue":"6","key":"pone.0273256.ref040","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-functional exchange-energy approximation with correct asymptotic behavior","volume":"38","author":"AD Becke","year":"1988","journal-title":"Physical Review A"},{"issue":"7","key":"pone.0273256.ref041","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density","volume":"37","author":"C Lee","year":"1988","journal-title":"Physical Review B"},{"issue":"1","key":"pone.0273256.ref042","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"HM Berman","year":"2000","journal-title":"Nucleic Acids Research"},{"key":"pone.0273256.ref043","article-title":"The PyMOL molecular graphics system","author":"WL DeLano","year":"2002","journal-title":"De-Lano Scientific, San Carlos, CA, USA"},{"key":"pone.0273256.ref044","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera-a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"Journal Computational Chemistry"},{"key":"pone.0273256.ref045","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-molecule library screening by docking with PyRx","volume":"1263","author":"S Dallakyan","year":"2015","journal-title":"Methods in Molecular Biology"},{"key":"pone.0273256.ref046","first-page":"267","article-title":"Discovering potential RNA dependent RNA polymerase inhibitors as prospective drugs against COVID-19: an in silico approach","volume":"12","author":"S Saha","year":"2021","journal-title":"Frontier Pharmacology"},{"key":"pone.0273256.ref047","year":"2017","journal-title":"Version ADS: 4.0, Accelrys, San Diego, USA"},{"key":"pone.0273256.ref048","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1021\/acs.jcim.0c00613","article-title":"Alchemical binding free energy calculations in AMBER20: Advances and best practices for drug discovery","volume":"60","author":"T-S Lee","year":"2020","journal-title":"Journal of Chemical Information and Modeling"},{"issue":"9","key":"pone.0273256.ref049","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general Amber force field","volume":"25","author":"J Wang","year":"2004","journal-title":"Journal of Compuataional Chemistry"},{"key":"pone.0273256.ref050","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0065-3233(03)66002-X","article-title":"Force fields for protein simulations","volume":"66","author":"JW Ponder","year":"2003","journal-title":"Advanced Protein Chemistry"},{"issue":"99","key":"pone.0273256.ref051","article-title":"Computer simulation of liquids","volume":"18","author":"CL Brooks","year":"1989","journal-title":"Journal of Solution Chemistry"},{"key":"pone.0273256.ref052","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5 log (N) method for Ewald sums in large systems","volume":"98","author":"T Darden","year":"1993","journal-title":"The Journal of Chemical Physics"},{"key":"pone.0273256.ref053","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of a system with constraints: of the cartesian equations of motion molecular dynamics of n-alkanes","volume":"23","author":"JP Ryckaert","year":"1977","journal-title":"Journal of Computational Physics"},{"issue":"7","key":"pone.0273256.ref054","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular","volume":"9","author":"DR Roe","year":"2013","journal-title":"Dyn Trajectory Data. Journal of Chemical Theory and Computation"},{"key":"pone.0273256.ref055","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An efficient program for end-state free energy calculations","volume":"8","author":"BR Miller","year":"2012","journal-title":"Journal of chemical theory and computation"},{"issue":"11","key":"pone.0273256.ref056","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1021\/ci300367a","article-title":"admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties","volume":"52","author":"F Cheng","year":"2012","journal-title":"Journal of Chemical Information Modeling"},{"key":"pone.0273256.ref057","doi-asserted-by":"crossref","first-page":"477","DOI":"10.35812\/CelluloseChemTechnol.2021.55.44","article-title":"Monosaccharide derivatives: synthesis, antimicrobial, pass, antiviral and molecular docking studies against SARS-COV-2 Mpro inhibitors","volume":"55","author":"F Yasmin","year":"2021","journal-title":"Journal of Cellulose Chemistry and Technology"},{"key":"pone.0273256.ref058","article-title":"P-glycoprotein inhibition for optimal drug delivery","author":"ML Amin","year":"2013","journal-title":"Drug Target Insights"},{"key":"pone.0273256.ref059","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/9780470125793.ch7","article-title":"Molecular electrostatic potentials and chemical reactivity","volume":"2","author":"P Politzer","year":"1991","journal-title":"Reviews in Computational Chemistry"},{"key":"pone.0273256.ref060","article-title":"Chemical applications of atomic and molecular electrostatic potentials: reactivity, structure, scattering, and energetics of organic, inorganic, and biological systems","author":"P Politzer","year":"2013","journal-title":"Springer Science & Business Media"},{"key":"pone.0273256.ref061","doi-asserted-by":"crossref","first-page":"e04502","DOI":"10.1016\/j.heliyon.2020.e04502","article-title":"SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) -A drug repurposing study","volume":"7","author":"J Ahmad","year":"2020","journal-title":"Heliyon"},{"key":"pone.0273256.ref062","first-page":"3204","article-title":"SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective","volume":"39","author":"AA Elfiky","year":"2021","journal-title":"Journal of Biomolecular Structure & Dynamics"},{"key":"pone.0273256.ref063","doi-asserted-by":"crossref","first-page":"105850","DOI":"10.1016\/j.bioorg.2022.105850","article-title":"Synthesis, antimicrobial, molecular docking and molecular dynamics studies of lauroyl thymidine analogs against SARS-CoV-2: POM study and identification of the pharmacophore sites","volume":"125","author":"MA Hosen","year":"2022","journal-title":"Bioorganic Chemistry"},{"issue":"2","key":"pone.0273256.ref064","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jgg.2020.02.001","article-title":"Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines","volume":"47","author":"X Liu","year":"2020","journal-title":"Journal of Genetics and Genomics"},{"issue":"5","key":"pone.0273256.ref065","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities.","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opinion on Drug Discovery"},{"key":"pone.0273256.ref066","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"CA Lipinski","year":"2001","journal-title":"Advanced Drug Delivery Reviews"},{"issue":"2","key":"pone.0273256.ref067","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10989-022-10365-6","article-title":"Exploring structural mechanism of COVID-19 treatment with glutathione as a potential peptide inhibitor to the main protease: molecular dynamics simulation and MM\/PBSA free energy calculations study.","volume":"28","author":"A Linani","year":"2022","journal-title":"International Journal for Peptide Research & Therapeutics"},{"issue":"6","key":"pone.0273256.ref068","first-page":"599","article-title":"BuildQSAR: a new computer program for QSAR analysis. quantitative structure\u2010activity relationships: An international journal devoted to fundamental and practical aspects of electroanalysis","volume":"19","author":"DBD Oliveira","year":"2001","journal-title":"Molcular Informatics"},{"key":"pone.0273256.ref069","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.molstruc.2019.07.053","article-title":"Synthesis, DFT and POM analyses of cytotoxicity activity of \u03b1-amidophosphonates derivatives: Identification of potential antiviral O,O-pharmacophore site","volume":"1197","author":"KT Rachedi","year":"2019","journal-title":"Journal of Molecular Structure"},{"key":"pone.0273256.ref070","doi-asserted-by":"crossref","first-page":"105587","DOI":"10.1016\/j.bioorg.2021.105587","article-title":"In vitro potential antiviral SARS-CoV-19- activity of natural product thy-mohydroquinone and dithymoquinone from Nigella sativia","volume":"120","author":"ER Esharkawy","year":"2022","journal-title":"Bioorganic Chemistry"},{"key":"pone.0273256.ref071","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2022.2029571","article-title":"In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site","volume":"40","author":"H Lafridi","year":"2022","journal-title":"Journal of Biomolecular Structure & Dynamics"},{"key":"pone.0273256.ref072","first-page":"1","article-title":"How to face COVID-19: Proposed treatments based on Remdesivir and Hydroxychloroquine in the presence of zinc sulfate","volume":"25","author":"T Ben Hadda","year":"2021","journal-title":"Docking\/DFT\/POM structural analysis, Journal of Biomolecular Structure & Dynamics"},{"key":"pone.0273256.ref073","doi-asserted-by":"crossref","first-page":"108246","DOI":"10.1016\/j.carres.2021.108246","article-title":"Synthesis, antiviral, and molecular docking studies of some novel 1,2,4-triazine nucleosides as potential bioactive compounds","volume":"500","author":"A Khodair","year":"2021","journal-title":"Carbohydrate Research"},{"issue":"1","key":"pone.0273256.ref074","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2174\/1573409916666191226110029","article-title":"Petra\/Osiris\/Molinspiration and molecular docking analyses of 3-hydroxy-indolin-2-one derivatives as potential antiviral agents","volume":"17","author":"TB Hadda","year":"2021","journal-title":"Current Computer-Aided Drug Design"},{"key":"pone.0273256.ref075","doi-asserted-by":"crossref","first-page":"103967","DOI":"10.1016\/j.compbiomed.2020.103967","article-title":"Immunoinformatics-guided design of an epitope-based vaccine against severe acute respiratory syndromecoronavirus spike glycoprotein","volume":"124","author":"A Rakib","year":"2020","journal-title":"Computers in Biology and Medicine"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0273256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T21:56:19Z","timestamp":1701467779000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0273256"}},"subtitle":[],"editor":[{"given":"Joazaizulfazli","family":"Jamalis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":75,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0273256","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]}}}