{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:18:19Z","timestamp":1787980699483,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"USDA-NIFA Animal Health and Disease Research","doi-asserted-by":"publisher","award":["NI26AHDRXXXXG063-0001"],"award-info":[{"award-number":["NI26AHDRXXXXG063-0001"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012768","name":"Long Island University","doi-asserted-by":"crossref","award":["40262"],"award-info":[{"award-number":["40262"]}],"id":[{"id":"10.13039\/100012768","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The main protease (MPro) of coronaviruses (CoVs) is an essential enzyme involved in viral replication and represents an attractive target for antiviral drug discovery. Based on the similar binding pocket residues within the MPro of different CoVs, this study aimed to identify potential inhibitors of SARS-CoV-2 MPro from PDB ID 6M2N using integrated computational approaches. Interaction-based pharmacophore modeling, virtual screening, molecular docking, MM-GBSA binding energy calculation, and molecular dynamics simulation (MDS) were performed using BIOVIA Discovery Studio. The validated pharmacophore model was utilized to screen the ZINC database, followed by docking and 100 ns MDS analyses of the top-ranked compounds. The pharmacophore model 01 demonstrated favorable predictive performance (AUC = 0.781). Virtual screening identified 483 compounds, from which 15 compounds were selected for docking studies. Among them, ZINC95473654 (Lig-1), ZINC95473725 (Lig-2), and ZINC08792368 (Lig-3) exhibited strong binding affinity toward MPro. Lig-1 demonstrated the best docking score and binding free energy, along with stable interactions with key catalytic residues HIS41, CYS145, and GLU166. MDS analyses further confirmed that Lig-1, Lig-2 and Lig-3 maintained stable conformations. The hydrogen bond distance monitoring and post MDS-MM-GBSA results suggest Lig-1 followed by Lig-3 as an inhibitor for MPro and persistent intermolecular interactions throughout the 100 ns simulation period. The findings suggest that Lig-1, followed by Lig-3, may serve as promising computational lead compounds targeting SARS-CoV-2 MPro, representing promising candidates for further experimental validation.<\/jats:p>","DOI":"10.3390\/ijms27177684","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:26:03Z","timestamp":1787837163000},"page":"7684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Potential SARS-CoV-2 Main Protease (MPro) Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1107-7428","authenticated-orcid":false,"given":"Mohd Yasir","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Digital Engineering and Artificial Intelligence, College of Science, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-1960","authenticated-orcid":false,"given":"Farah","family":"Maarfi","sequence":"additional","affiliation":[{"name":"Department of Digital Engineering and Artificial Intelligence, College of Science, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid Ullah","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, 720 Northern Boulevard, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-0008","authenticated-orcid":false,"given":"Nithyadevi","family":"Duraisamy","sequence":"additional","affiliation":[{"name":"Department of Digital Engineering and Artificial Intelligence, College of Science, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Cherkaoui","sequence":"additional","affiliation":[{"name":"Department of Digital Engineering and Artificial Intelligence, College of Science, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-5820","authenticated-orcid":false,"given":"Maged Gomaa","family":"Hemida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, 720 Northern Boulevard, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Comparative analysis of the genome structure and organization of the Middle East respiratory syndrome coronavirus (MERS-CoV) 2012 to 2019 revealing evidence for virus strain barcoding, zoonotic transmission, and selection pressure","volume":"31","author":"Hemida","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hemida, M.G., Egamberdieva, D., and Malik, Y.S. (2023). Editorial: Coronaviruses from the One Health perspective. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1338529"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shah, A.U., Esparza, B., Illanes, O., and Hemida, M.G. (2025). Comparative Genome Sequencing Analysis of Some Novel Feline Infectious Peritonitis Viruses Isolated from Some Feral Cats in Long Island. Viruses, 17.","DOI":"10.3390\/v17020209"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110313","DOI":"10.1016\/j.virol.2024.110313","article-title":"Isolation and molecular characterization of an enteric isolate of the genotype-Ia bovine coronavirus with notable mutations in the receptor binding domain of the spike glycoprotein","volume":"603","author":"Shah","year":"2025","journal-title":"Virology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105723","DOI":"10.1016\/j.meegid.2025.105723","article-title":"Some novel field isolates belonging to lineage-1 of the genotype GI-avian infectious bronchitis virus (AIBV) show strong evidence of recombination with field\/vaccinal strains","volume":"129","author":"Shah","year":"2025","journal-title":"Infect. Genet. Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4756404","DOI":"10.1155\/2019\/4756404","article-title":"Evidence of Peste des petits Ruminants\u2019 Virus in Dromedary Camels in the Kingdom of Saudi Arabia between 2014 and 2016","volume":"2019","author":"Hemida","year":"2019","journal-title":"Vet. Med. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100102","DOI":"10.1016\/j.onehlt.2019.100102","article-title":"Some One Health based control strategies for the Middle East respiratory syndrome coronavirus","volume":"8","author":"Hemida","year":"2019","journal-title":"One Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100127","DOI":"10.1016\/j.onehlt.2020.100127","article-title":"The SARS-CoV-2 outbreak from a one health perspective","volume":"10","author":"Hemida","year":"2020","journal-title":"One Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6491738","DOI":"10.1155\/2019\/6491738","article-title":"Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development","volume":"2019","author":"Mubarak","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Al-Mubarak, A.I.A., Al-Kubati, A.A.G., Sheikh, A., Abdelaziz, A.M., Hussen, J., Kandeel, M., Falemban, B., and Hemida, M.G. (2024). Detection of Avian Orthoavulavirus-1 genotypes VI.2.1 and VII.1.1 with neuro-viscerotropic tropism in some backyard pigeons (Columbidae) in Eastern Saudi Arabia. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1352636"},{"key":"ref_11","first-page":"1246","article-title":"Evidence of the circulation of avian metapneumovirus in domestic backyard chickens in Eastern Saudi Arabia in 2019","volume":"16","author":"Hussen","year":"2023","journal-title":"Vet. World"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"424","DOI":"10.14202\/vetworld.2019.424-433","article-title":"Infectious bronchitis virus from chickens in Al-Hasa, Saudi Arabia 2015\u20132016","volume":"12","author":"Alsultan","year":"2019","journal-title":"Vet. World"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1073\/pnas.1718769115","article-title":"MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity","volume":"115","author":"Chu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1002\/jmv.26926","article-title":"The next-generation coronavirus diagnostic techniques with particular emphasis on the SARS-CoV-2","volume":"93","author":"Hemida","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s13337-017-0375-7","article-title":"Molecular characterization and phylogenetic analyses of virulent infectious bronchitis viruses isolated from chickens in Eastern Saudi Arabia","volume":"28","author":"Hemida","year":"2017","journal-title":"Virusdisease"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e9035","DOI":"10.7717\/peerj.9035","article-title":"Prevalence and molecular characterization of some circulating strains of the peste-des-petits-ruminants virus in Saudi Arabia between 2014\u20132016","volume":"8","author":"Hemida","year":"2020","journal-title":"PeerJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1002\/vms3.760","article-title":"Betaretrovirus infections in dromedary camels in Saudi Arabia","volume":"8","author":"Hemida","year":"2022","journal-title":"Vet. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1111\/tbed.12630","article-title":"Coronavirus infections in horses in Saudi Arabia and Oman","volume":"64","author":"Hemida","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/evj.13001","article-title":"Evidence of equine influenza A (H3N8) activity in horses from Eastern and Central Saudi Arabia: 2013\u20132015","volume":"51","author":"Hemida","year":"2019","journal-title":"Equine Vet. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/01652176.2018.1539568","article-title":"Foot-and-mouth disease virus O\/ME-SA\/Ind 2001 lineage outbreak in vaccinated Holstein Friesian cattle in Saudi Arabia in 2016","volume":"38","author":"Hemida","year":"2018","journal-title":"Vet. Q."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/cmdc.202000924","article-title":"A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors*","volume":"16","author":"Yang","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102667","DOI":"10.1016\/j.sbi.2023.102667","article-title":"Structural biology of SARS-CoV-2 M(pro) and drug discovery","volume":"82","author":"Duan","year":"2023","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Duraisamy, N., Khan, M.Y., Shah, A.U., Elalaoui, R.N., Cherkaoui, M., and Hemida, M.G. (2024). Machine learning tools used for mapping some immunogenic epitopes within the major structural proteins of the bovine coronavirus (BCoV) and for the in silico design of the multiepitope-based vaccines. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1468890"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Khan, M.Y., Shah, A.U., Duraisamy, N., Cherkaoui, M., and Hemida, M.G. (2025). Repurposing of Some Nucleoside Analogs Targeting Some Key Proteins of the Avian H5N1 Clade 2.3.4.4b to Combat the Circulating HPAI in Birds: An In Silico Approach. Viruses, 17.","DOI":"10.20944\/preprints202506.0522.v1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khan, M.Y., Shah, A.U., Duraisamy, N., ElAlaoui, R.N., Cherkaoui, M., and Hemida, M.G. (2025). Leveraging Artificial Intelligence and Gene Expression Analysis to Identify Some Potential Bovine Coronavirus (BCoV) Receptors and Host Cell Enzymes Potentially Involved in the Viral Replication and Tissue Tropism. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031328"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1529\/biophysj.106.091736","article-title":"Reversible unfolding of the severe acute respiratory syndrome coronavirus main protease in guanidinium chloride","volume":"92","author":"Chang","year":"2007","journal-title":"Biophys. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14958","DOI":"10.1021\/bi0490237","article-title":"Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus main protease","volume":"43","author":"Chou","year":"2004","journal-title":"Biochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s11224-022-02089-6","article-title":"Structural differences in 3C-like protease (Mpro) from SARS-CoV and SARS-CoV-2: Molecular insights revealed by Molecular Dynamics Simulations","volume":"34","author":"Parmar","year":"2023","journal-title":"Struct. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s42003-022-03090-9","article-title":"Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay","volume":"5","author":"Narayanan","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1038\/s41467-020-18233-x","article-title":"Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease","volume":"11","author":"Fu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fukumoto, Y., Suzuki, N., Hara, R., Tanaka, Y.K., and Ogra, Y. (2024). Development of a Biosafety Level 1 Cellular Assay for Identifying Small-Molecule Antivirals Targeting the Main Protease of SARS-CoV-2: Evaluation of Cellular Activity of GC376, Boceprevir, Carmofur, Ebselen, and Selenoneine. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115767"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1038\/s41467-020-16954-7","article-title":"Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography","volume":"11","author":"Kneller","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41594-020-0440-6","article-title":"Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur","volume":"27","author":"Jin","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1126\/science.1085658","article-title":"Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs","volume":"300","author":"Anand","year":"2003","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1128\/JVI.02680-07","article-title":"Mechanism for controlling the dimer-monomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3C-like protease","volume":"82","author":"Shi","year":"2008","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/ci049885e","article-title":"LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters","volume":"45","author":"Wolber","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tran, Q.H., Nguyen, Q.T., Vo, N.Q., Mai, T.T., Tran, T.T., Tran, T.D., Le, M.T., Trinh, D.T., and Thai, K.M. (2022). Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266632"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of M(pro) from SARS-CoV-2 and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jiang, S., Yuan, J., Li, Q., Song, Z., Cao, L., Song, Z., and Zhang, X. (2026). The structure and function of membrane protein in coronavirus infection and its applications in the development of vaccines and therapeutic drugs. Front. Microbiol., 17.","DOI":"10.3389\/fmicb.2026.1762041"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e19744","DOI":"10.7717\/peerj.19744","article-title":"Identification of potential inhibitors of the main protease from feline infectious peritonitis virus using molecular docking and dynamic simulation approaches","volume":"13","author":"Khan","year":"2025","journal-title":"PeerJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104697","DOI":"10.1016\/j.jbc.2023.104697","article-title":"SARS-CoV-2 polyprotein substrate regulates the stepwise M(pro) cleavage reaction","volume":"299","author":"Narwal","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127377","DOI":"10.1016\/j.bmcl.2020.127377","article-title":"The SARS-CoV-2 main protease as drug target","volume":"30","author":"Ullrich","year":"2020","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"106545","DOI":"10.1016\/j.ijantimicag.2022.106545","article-title":"Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: A systematic review and meta-analysis of randomised controlled trials","volume":"59","author":"Hsu","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Motyan, J.A., Mahdi, M., Hoffka, G., and Tozser, J. (2022). Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073507"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Melano, I., Lo, Y.C., and Su, W.C. (2023). Characterization of host substrates of SARS-CoV-2 main protease. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1251705"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42751","DOI":"10.1038\/srep42751","article-title":"Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening","volume":"7","author":"Temml","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"28097","DOI":"10.1038\/s41598-024-78330-5","article-title":"Identification of novel PAD2 inhibitors using pharmacophore-based virtual screening, molecular docking, and MD simulation studies","volume":"14","author":"Jha","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16922","DOI":"10.1021\/acs.jmedchem.1c00409","article-title":"Perspectives on SARS-CoV-2 Main Protease Inhibitors","volume":"64","author":"Gao","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/157340910790980151","article-title":"Pharmacophore based drug design approach as a practical process in drug discovery","volume":"6","author":"Gao","year":"2010","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Giordano, D., Biancaniello, C., Argenio, M.A., and Facchiano, A. (2022). Drug Design by Pharmacophore and Virtual Screening Approach. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050646"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"108427","DOI":"10.1016\/j.compbiolchem.2025.108427","article-title":"Discovery of natural MCL1 inhibitors using pharmacophore modelling, QSAR, docking, ADMET, molecular dynamics, and DFT analysis","volume":"117","author":"Das","year":"2025","journal-title":"Comput. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ejmech.2018.03.004","article-title":"Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element","volume":"150","author":"Kim","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s11224-022-01959-3","article-title":"Antiviral phytocompounds \u201cellagic acid\u201d and \u201c(+)-sesamin\u201d of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction","volume":"33","author":"Umar","year":"2022","journal-title":"Struct. Chem."},{"key":"ref_54","first-page":"51","article-title":"Targeting SARS-CoV-2 main protease (Mpro) and human ACE-2: A virtual screening of carotenoids and polyphenols from tomato (Solanum lycopersicum L.) to combat COVID-19","volume":"2","author":"Ahmad","year":"2024","journal-title":"Intell. Pharm."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ashraf, Z., Rasool, R., Hassan, M., Ahsan, H., Afzal, S., Afzal, K., Cho, H., and Kim, S.J. (2016). Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen-Antioxidant Mutual Prodrugs. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122151"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1080\/07391102.2020.1821785","article-title":"A dynamic simulation study of FDA drug from zinc database against COVID-19 main protease receptor","volume":"40","author":"Mathpal","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"201","DOI":"10.22146\/ijc.57012","article-title":"Design of New Quinazoline Derivative as EGFR (Epidermal Growth Factor Receptor) Inhibitor through Molecular Docking and Dynamics Simulation","volume":"21","author":"Rasyid","year":"2021","journal-title":"Indones. J. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e14120","DOI":"10.7717\/peerj.14120","article-title":"Identification of 1H-purine-2,6-dione derivative as a potential SARS-CoV-2 main protease inhibitor: Molecular docking, dynamic simulations, and energy calculations","volume":"10","author":"Nada","year":"2022","journal-title":"PeerJ"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e202400778","DOI":"10.1002\/cbdv.202400778","article-title":"A Structure-Based Design Strategy with Pyrazole-Pyridine Derivatives Targeting TNFalpha as Anti-Inflammatory Agents: E-Pharmacophore, Dynamic Simulation, Synthesis and In Vitro Evaluation","volume":"21","author":"Halder","year":"2024","journal-title":"Chem. Biodivers."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1021\/ci300083r","article-title":"Protein-ligand-based pharmacophores: Generation and utility assessment in computational ligand profiling","volume":"52","author":"Meslamani","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Maarfi, F., Cherkaoui, M., Afreen, S., and Khan, M.Y. (2026). Blocking ASIP to Protect MC1R Signaling and Mitigate Melanoma Risk: An In Silico Study. Pharmaceuticals, 19.","DOI":"10.3390\/ph19010114"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10910-023-01537-w","article-title":"Identification of potential oral cancer drugs as Bcl-2 inhibitors from known anti-neoplastic agents through docking studies","volume":"62","author":"Raychaudhury","year":"2024","journal-title":"J. Math. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"133952","DOI":"10.1016\/j.molstruc.2022.133952","article-title":"Identification of new anti-cancer agents against CENTERIN: Structure-based virtual screening, AutoDock and binding free energy studies","volume":"1270","author":"Nakkala","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1080\/07391102.2022.2074142","article-title":"Computational assessment of Withania somnifera phytomolecules as putative inhibitors of Mycobacterium tuberculosis CTP synthase PyrG","volume":"41","author":"Singh","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"29321","DOI":"10.1038\/s41598-025-13943-y","article-title":"Structure based in silico screening of natural Vitamin D analogs for targeted and safer treatment of resistant multiple sclerosis","volume":"15","author":"Lohani","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_67","first-page":"37","article-title":"Molecular dynamics simulations: Advances and applications","volume":"8","author":"Hospital","year":"2015","journal-title":"Adv. Appl. Bioinform. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1038\/s41467-020-18096-2","article-title":"Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication","volume":"11","author":"Vuong","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41422-020-0356-z","article-title":"Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease","volume":"30","author":"Ma","year":"2020","journal-title":"Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","article-title":"Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19","volume":"65","author":"Unoh","year":"2022","journal-title":"J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:26:06Z","timestamp":1787977566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":71,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177684"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177684","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}