{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:51:08Z","timestamp":1785909068798,"version":"3.56.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100010104","name":"Tianjin Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["25JCZDJC00490"],"award-info":[{"award-number":["25JCZDJC00490"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Computational Biology and Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.compbiolchem.2026.109199","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:50:49Z","timestamp":1781592649000},"page":"109199","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["PRISM-Gen: A physics-informed multi-fidelity framework for broad-spectrum coronavirus mpro inhibitor discovery"],"prefix":"10.1016","volume":"124","author":[{"given":"Hongmei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjia","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.compbiolchem.2026.109199_bib1","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1021\/acs.jctc.8b01176","article-title":"GFN2-xTB\u2014An accurate and broadly parametrized self-consistent tight-binding quantum chemical method with multipole electrostatics and density-dependent dispersion contributions","volume":"15","author":"Bannwarth","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib2","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","article-title":"Density-functional thermochemistry. III. The role of exact exchange","volume":"98","author":"Becke","year":"1993","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib3","first-page":"263","article-title":"Robust solutions of optimization problems affected by uncertain probabilities","volume":"147","author":"Ben-Tal","year":"2013","journal-title":"Math. Program."},{"issue":"3","key":"10.1016\/j.compbiolchem.2026.109199_bib4","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1080\/07391102.2023.2291549","article-title":"Silico Development of Potential InhA Inhibitors through 3D-QSAR analysis, virtual screening, and molecular dynamics","volume":"43","author":"Bhaskar","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nchem.1243","article-title":"Quantifying the chemical beauty of drugs","volume":"4","author":"Bickerton","year":"2012","journal-title":"Nat. Chem."},{"issue":"5","key":"10.1016\/j.compbiolchem.2026.109199_bib6","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1608","article-title":"Generative models for molecular discovery: recent advances and challenges","volume":"12","author":"Bilodeau","year":"2022","journal-title":"WIREs Comput. Mol. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1021\/ci9803381","article-title":"Unsupervised data base clustering based on daylight\u2019s fingerprint and tanimoto similarity: a fast and automated way to cluster small and large data sets","volume":"39","author":"Butina","year":"1999","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2012.10.053","article-title":"Design, synthesis and crystallographic analysis of nitrile-based peptidomimetic inhibitors for SARS-CoV main protease","volume":"59","author":"Chuck","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib9","series-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib10","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1214\/20-AOS2004","article-title":"Learning models with uniform performance via distributionally robust optimization","volume":"49","author":"Duchi","year":"2021","journal-title":"Ann. Stat."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1758-2946-1-8","article-title":"Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions","volume":"1","author":"Ertl","year":"2009","journal-title":"J. Chemin.-."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib12","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1021\/acscentsci.7b00572","article-title":"Automatic chemical design using a data-driven continuous representation of molecules","volume":"4","author":"G\u00f3mez-Bombarelli","year":"2018","journal-title":"ACS Cent. Sci."},{"issue":"5","key":"10.1016\/j.compbiolchem.2026.109199_bib13","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1021\/acs.jctc.7b00118","article-title":"A robust and accurate tight-binding quantum chemical method for structures, vibrational frequencies, and noncovalent interactions of large molecular systems parametrized for all spd-block elements (Z = 1\u201386)","volume":"13","author":"Grimme","year":"2017","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib14","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","article-title":"Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94","volume":"17","author":"Halgren","year":"1996","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib15","article-title":"Therapeutics data commons: machine learning datasets and tasks for drug discovery and development","author":"Huang","year":"2021","journal-title":"Proc. NeurIPS Datasets Benchmarks Track."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s42004-025-01640-w","article-title":"Leveraging Tree-Transformer VAE with fragment tokenization for high-performance large chemical model generation","volume":"8","author":"Inukai","year":"2025","journal-title":"Commun. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib17","first-page":"2323","article-title":"Junction tree variational autoencoder for molecular graph generation","author":"Jin","year":"2018","journal-title":"Proc. Int. Conf. Mach. Learn."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib19","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1126\/science.220.4598.671","article-title":"Optimization by simulated annealing","volume":"220","author":"Kirkpatrick","year":"1983","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib20","unstructured":"Landrum, G. RDKit: Open-Source Cheminformatics. \u3008http:\/\/www.rdkit.org\u3009 (Accessed 2024-05-20)."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open babel: an open chemical toolbox","volume":"3","author":"O\u2019Boyle","year":"2011","journal-title":"J. Chemin.-."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib23","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An Oral SARS-CoV-2Mpro inhibitor clinical candidate for the treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib24","series-title":"Density-Functional Theory of Atoms and Molecules","author":"Parr","year":"1989"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib25","first-page":"2825","article-title":"Scikit-learn: machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"issue":"15","key":"10.1016\/j.compbiolchem.2026.109199_bib26","doi-asserted-by":"crossref","first-page":"8803","DOI":"10.1080\/07391102.2024.2445169","article-title":"Is it feasible to use ai-based drug design methods in the process of generating effective COVID-19 Inhibitors? A validation study using molecular docking, molecular simulation, and pharmacophore methods","volume":"43","author":"Qu","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib27","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1021\/acs.jcim.5b00654","article-title":"Better informed distance geometry: using what we know to improve conformation generation","volume":"55","author":"Riniker","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib28","article-title":"Distributionally robust neural networks for group shifts: on the importance of regularization for worst-case generalization","author":"Sagawa","year":"2020","journal-title":"Proc. Int. Conf. Learn. Represent."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib29","series-title":"Advances in Neural Information Processing Systems 36 (NeurIPS 2023)","article-title":"Equivariant Flow Matching with Hybrid Probability Transport for 3D Molecule Generation","author":"Song","year":"2023"},{"issue":"1","key":"10.1016\/j.compbiolchem.2026.109199_bib30","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1340","article-title":"PySCF: the python-based simulations of chemistry framework","volume":"8","author":"Sun","year":"2018","journal-title":"WIREs Comput. Mol. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib31","doi-asserted-by":"crossref","first-page":"19403","DOI":"10.1074\/jbc.M115.651463","article-title":"Ligand-induced dimerization of middle east respiratory syndrome (MERS) Coronavirus nsp5 Protease (3CLpro)","volume":"290","author":"Tomar","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib32","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib33","doi-asserted-by":"crossref","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":"10.1016\/j.compbiolchem.2026.109199_bib34","series-title":"Proceedings of the 11th International Conference on Learning Representations (ICLR); Kigali, Rwanda","article-title":"DiGress: discrete denoising diffusion for graph generation","author":"Vignac","year":"2023"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib35","first-page":"7978","article-title":"Design of wide-spectrum inhibitors targeting coronavirus main proteases","volume":"102","author":"Yang","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.compbiolchem.2026.109199_bib36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal Structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-Ketoamide Inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.compbiolchem.2026.109199_bib37","series-title":"Proceedings of the 11th International Conference on Learning Representations (ICLR); Kigali, Rwanda","article-title":"Uni-Mol: A Universal 3D molecular representation learning framework","author":"Zhou","year":"2023"}],"container-title":["Computational Biology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1476927126003269?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1476927126003269?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:32:06Z","timestamp":1785907926000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1476927126003269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":37,"alternative-id":["S1476927126003269"],"URL":"https:\/\/doi.org\/10.1016\/j.compbiolchem.2026.109199","relation":{},"ISSN":["1476-9271"],"issn-type":[{"value":"1476-9271","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PRISM-Gen: A physics-informed multi-fidelity framework for broad-spectrum coronavirus mpro inhibitor discovery","name":"articletitle","label":"Article Title"},{"value":"Computational Biology and Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.compbiolchem.2026.109199","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109199"}}