Computationally driven discovery of SARS-CoV-2 Mproinhibitors: from design to experimental validation

Léa El Khoury, Zhifeng Jing, Alberto Cuzzolin, Alessandro Deplano, Daniele Loco, Boris Sattarov, Florent Hédin, Sebastian Wendeborn, Chris Ho, Dina El Ahdab, Theo Jaffrelot Inizan, Mattia Sturlese, Alice Sosic, Martina Volpiana, Angela Lugato, Marco Barone, Barbara Gatto, Maria Ludovica Macchia, Massimo Bellanda, Roberto Battistutta, Cristiano Salata, Ivan Kondratov, Rustam Iminov, Andrii Khairulin, Yaroslav Mykhalonok, Anton Pochepko, Volodymyr Chashka-Ratushnyi, Iaroslava Kos, Stefano Moro, Matthieu Montes, Pengyu Ren, Jay W. Ponder, Louis Lagardère, Jean-Philip Piquemal and Davide Sabbadin

Chem. Sci., 2022, 13, 3674
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Scalable hybrid deep neural networks/polarizable potentials biomolecular simulations including long-range effects

Théo Jaffrelot Inizan, Thomas Plé, Olivier Adjoua, Pengyu Ren, Hatice Gökcan, Olexandr Isayev, Louis Lagardère and Jean-Philip Piquemal

Chem. Sci., 2023, 14, 5438
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The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies

Nanik Siti Aminah, Muhammad Ikhlas Abdjan, Andika Pramudya Wardana, Alfinda Novi Kristanti, Imam Siswanto, Khusna Arif Rakhman and Yoshiaki Takaya

RSC Adv., 2021, 11, 39455
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Water–glycan interactions drive the SARS-CoV-2 spike dynamics: insights into glycan-gate control and camouflage mechanisms

Marharyta Blazhynska, Louis Lagardère, Chengwen Liu, Olivier Adjoua, Pengyu Ren and Jean-Philip Piquemal

Chem. Sci., 2024, 15, 14177
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Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

Dénes Berta, Magd Badaoui, Sam Alexander Martino, Pedro J. Buigues, Andrei V. Pisliakov, Nadia Elghobashi-Meinhardt, Geoff Wells, Sarah A. Harris, Elisa Frezza and Edina Rosta

Chem. Sci., 2021, 12, 13492
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Water-Triggered, Irreversible Conformational Change of SARS-CoV-2 Main Protease on Passing from the Solid State to Aqueous Solution

Narjes Ansari, Valerio Rizzi, Paolo Carloni and Michele Parrinello

J. Am. Chem. Soc., 2021, 143, 12930
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Unveiling the Full Dynamical and Reactivity Profiles of Acetylcholinesterase: A Comprehensive All-Atom Investigation

Frédéric Célerse, Louis Lagardère, Yasmine Bouchibti, Florian Nachon, Laurent Verdier, Jean-Philip Piquemal and Etienne Derat

ACS Catal., 2024, 14, 1785
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A Reflection on the Use of Molecular Simulation to Respond to SARS-CoV-2 Pandemic Threats

Lorenzo Casalino, Carlos A. Ramos-Guzmán, Rommie E. Amaro, Carlos Simmerling, Alessio Lodola, Adrian J. Mulholland, Katarzyna Świderek and Vicent Moliner

J. Phys. Chem. Lett., 2025, 16, 3249
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Routine Molecular Dynamics Simulations Including Nuclear Quantum Effects: From Force Fields to Machine Learning Potentials

Thomas Plé, Nastasia Mauger, Olivier Adjoua, Théo Jaffrelot Inizan, Louis Lagardère, Simon Huppert and Jean-Philip Piquemal

J. Chem. Theory Comput., 2023, 19, 1432
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k-Nearest Neighbor Adaptive Sampling, a Simple Tool to Efficiently Explore Conformational Space

Evianne Rovers, Anvith Thudi, Jérôme Hénin, Chris J. Maddison and Matthieu Schapira

J. Chem. Theory Comput., 2025, 21, 8267
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Benchmarking the Ability of Common Docking Programs to Correctly Reproduce and Score Binding Modes in SARS-CoV-2 Protease Mpro

Shani Zev, Keren Raz, Renana Schwartz, Reem Tarabeh, Prashant Kumar Gupta and Dan T. Major

J. Chem. Inf. Model., 2021, 61, 2957
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Precursors of Viral Proteases as Distinct Drug Targets

Taťána Majerová and Pavel Novotný

Viruses, 2021, 13, 1981
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Allosteric Binding Sites of the SARS-CoV-2 Main Protease: Potential Targets for Broad-Spectrum Anti-Coronavirus Agents

Lara Alzyoud, Mohammad A Ghattas and Noor Atatreh

DDDT, 2022, Volume 16, 2463
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Performance of the bond capacity model for charge polarization in classical molecular dynamics

Elton Oyarzua and Frank Jensen

The Journal of Chemical Physics, 2025, 163
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Accelerated Simulations of Molecular Systems through Learning of Effective Dynamics

Pantelis R. Vlachas, Julija Zavadlav, Matej Praprotnik and Petros Koumoutsakos

J. Chem. Theory Comput., 2022, 18, 538
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Lambda-ABF-OPES: Faster Convergence with High Accuracy in Alchemical Free Energy Calculations

Narjes Ansari, Zhifeng Francis Jing, Antoine Gagelin, Florent Hédin, Félix Aviat, Jérôme Hénin, Jean-Philip Piquemal and Louis Lagardère

J. Phys. Chem. Lett., 2025, 16, 4626
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Molecular docking and dynamics study to explore phytochemical ligand molecules against the main protease of SARS-CoV-2 from extensive phytochemical datasets

Shafi Mahmud, Mohasana Akter Mita, Suvro Biswas, Gobindo Kumar Paul, Maria Meha Promi, Shamima Afrose, Robiul Hasan, Sharmin Sultana Shimu, Shahriar Zaman, Salah Uddin, Trina Ekawati Tallei, Talha Bin Emran and Abu Saleh

Expert Review of Clinical Pharmacology, 2021, 14, 1305
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Elucidation of Cryptic and Allosteric Pockets within the SARS-CoV-2 Main Protease

Terra Sztain, Rommie Amaro and J. Andrew McCammon

J. Chem. Inf. Model., 2021, 61, 3495
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An Efficient Gaussian-Accelerated Molecular Dynamics (GaMD) Multilevel Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems

Frédéric Célerse, Théo Jaffrelot Inizan, Louis Lagardère, Olivier Adjoua, Pierre Monmarché, Yinglong Miao, Etienne Derat and Jean-Philip Piquemal

J. Chem. Theory Comput., 2022, 18, 968
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Targeting RNA with small molecules using state-of-the-art methods provides highly predictive affinities of riboswitch inhibitors

Narjes Ansari, Chengwen Liu, Florent Hédin, Jérôme Hénin, Jay W. Ponder, Pengyu Ren, Jean-Philip Piquemal, Louis Lagardère and Krystel El Hage

Commun Biol, 2025, 8
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AMOEBA Polarizable Molecular Dynamics Simulations of Guanine Quadruplexes: From the c-Kit Proto-Oncogene to HIV-1

Dina El Ahdab, Louis Lagardère, Zeina Hobaika, Théo Jaffrelot Inizan, Frédéric Célerse, Nohad Gresh, Richard G. Maroun and Jean-Philip Piquemal

J. Chem. Inf. Model., 2025, 65, 4488
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Structural insights into the substrate‐binding site of main protease for the structure‐based COVID‐19 drug discovery

Rohoullah Firouzi, Mitra Ashouri and Mohammad Hossein Karimi‐Jafari

Proteins, 2022, 90, 1090
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Pharmacophore Model for SARS-CoV-2 3CLpro Small-Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors

Enrico Glaab, Ganesh Babu Manoharan and Daniel Abankwa

J. Chem. Inf. Model., 2021, 61, 4082
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Accelerating Molecular Dynamics Simulations with Foundation Neural Network Models Using Multiple Time Steps and Distillation

Côme Cattin, Thomas Plé, Olivier Adjoua, Nicolaï Gouraud, Louis Lagardère and Jean-Philip Piquemal

J. Phys. Chem. Lett., 2026, 17, 1288
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Pre‐exascale HPC approaches for molecular dynamics simulations. Covid‐19 research: A use case

Miłosz Wieczór, Vito Genna, Juan Aranda, Rosa M. Badia, Josep Lluís Gelpí, Vytautas Gapsys, Bert L. de Groot, Erik Lindahl, Martí Municoy, Adam Hospital and Modesto Orozco

WIREs Comput Mol Sci, 2023, 13
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Identification of Protein Cryptic Sites via Conformational Dynamics Capturing and Water-Based Pocket Characterization in Molecular Dynamics Simulations

Tianming Qu, Steven L. Austin, Lianqing Zheng, James Zhang and Wei Yang

J. Chem. Theory Comput., 2025, 21, 8571
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Carboxylic submetabolome-driven signature characterization of COVID-19 asymptomatic infection

Jing Xu, Yu Yuan, Yao-Yu Chen, Cai-Feng Xiong, Zheng Zhang and Yu-Qi Feng

Talanta, 2022, 239, 123086
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High‐Resolution Molecular‐Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2)

Quentin Delobelle, Théo Jaffrelot Inizan, Olivier Adjoua, Louis Lagardère, Frédéric Célerse, Vincent Maréchal and Jean‐Philip Piquemal

Chemistry A European J, 2025, 31
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Accuracy and precision of binding free energy prediction for a tacrine related lead inhibitor of acetylcholinesterase with an arsenal of supercomputerized molecular modelling methods: a comparative study

Rafael Dolezal

Journal of Biomolecular Structure and Dynamics, 2022, 40, 11291
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Dynamics of 5R-Tg Base Flipping in DNA Duplexes Based on Simulations─Agreement with Experiments and Beyond

Shu dong Wang, Leif A. Eriksson and Ru bo Zhang

J. Chem. Inf. Model., 2022, 62, 386
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A polarisable force field for bio-compatible ionic liquids based on amino acids anions

Stefano Russo and Enrico Bodo

Molecular Simulation, 2022, 48, 1650
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Dynamic pre-structuration of lipid nanodomain-segregating remorin proteins

Zeren Xu, Adrien Schahl, Marie-Dominique Jolivet, Anthony Legrand, Axelle Grélard, Mélanie Berbon, Estelle Morvan, Louis Lagardere, Jean-Philip Piquemal, Antoine Loquet, Véronique Germain, Matthieu Chavent, Sébastien Mongrand and Birgit Habenstein

Commun Biol, 2024, 7
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Unveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations

Xiaoxia Gu, Xiaotian Zhang, Xueke Zhang, Xinyu Wang, Weiguang Sun, Yonghui Zhang and Zhengxi Hu

Nat. Prod. Bioprospect., 2025, 15
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The Conformational Space of the SARS-CoV-2 Main Protease Active Site Loops Is Determined by Ligand Binding and Interprotomer Allostery

Ethan Lee and Sarah Rauscher

Biochemistry, 2025, 64, 32
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Histidine 73 methylation coordinates β-actin plasticity in response to key environmental factors

Adrien Schahl, Louis Lagardère, Brandon Walker, Pengyu Ren, Hugo Wioland, Maya Ballet, Antoine Jégou, Matthieu Chavent and Jean-Philip Piquemal

Nat Commun, 2025, 16
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Unveiling mutation effects on the structural dynamics of the main protease from SARS-CoV-2 with hybrid simulation methods

P. Gasparini, E.A. Philot, S.Q. Pantaleão, N.E.S.M. Torres-Bonfim, A. Kliousoff, R.C.N. Quiroz, D. Perahia, R.P. Simões, A.J. Magro and A.L. Scott

Journal of Molecular Graphics and Modelling, 2023, 121, 108443
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A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers

Rafael E. O. Rocha, Elton J. F. Chaves, Pedro H. C. Fischer, Leon S. C. Costa, Igor Barden Grillo, Luiz E. G. da Cruz, Fabiana C. Guedes, Carlos H. da Silveira, Marcus T. Scotti, Alex D. Camargo, Karina S. Machado, Adriano V. Werhli, Rafaela S. Ferreira, Gerd B. Rocha and Leonardo H. F. de Lima

Journal of Biomolecular Structure and Dynamics, 2022, 40, 9214
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MD simulations indicate Omicron P132H of SARS-CoV-2 Mpro is a potential allosteric mutant involved in modulating the dynamics of catalytic site entry loop

Zahoor Ahmad Bhat, Mohd Muzammil Khan, Ayyub Rehman, Jawed Iqbal, B.S. Sanjeev and Arumugam Madhumalar

International Journal of Biological Macromolecules, 2024, 262, 130077
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Tinker-HP: Accelerating Molecular Dynamics Simulations of Large Complex Systems with Advanced Point Dipole Polarizable Force Fields Using GPUs and Multi-GPU Systems

Olivier Adjoua, Louis Lagardère, Luc-Henri Jolly, Arnaud Durocher, Thibaut Very, Isabelle Dupays, Zhi Wang, Théo Jaffrelot Inizan, Frédéric Célerse, Pengyu Ren, Jay W. Ponder and Jean-Philip Piquemal

J. Chem. Theory Comput., 2021, 17, 2034
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Interfacial Water Many-Body Effects Drive Structural Dynamics and Allosteric Interactions in SARS-CoV-2 Main Protease Dimerization Interface

Dina El Ahdab, Louis Lagardère, Théo Jaffrelot Inizan, Fréderic Célerse, Chengwen Liu, Olivier Adjoua, Luc-Henri Jolly, Nohad Gresh, Zeina Hobaika, Pengyu Ren, Richard G. Maroun and Jean-Philip Piquemal

J. Phys. Chem. Lett., 2021, 12, 6218
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pH profiles of 3-chymotrypsin-like protease (3CLpro) from SARS-CoV-2 elucidate its catalytic mechanism and a histidine residue critical for activity

Kenana Al Adem, Juliana C. Ferreira, Samar Fadl and Wael M. Rabeh

Journal of Biological Chemistry, 2023, 299, 102790
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Advancing Force Fields Parameterization: A Directed Graph Attention Networks Approach

Gong Chen, Théo Jaffrelot Inizan, Thomas Plé, Louis Lagardère, Jean-Philip Piquemal and Yvon Maday

J. Chem. Theory Comput., 2024, 20, 5558
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Targeting the Major Groove of the Palindromic d(GGCGCC)2 Sequence by Oligopeptide Derivatives of Anthraquinone Intercalators

Krystel El Hage, Giovanni Ribaudo, Louis Lagardère, Alberto Ongaro, Philippe H. Kahn, Luc Demange, Jean-Philip Piquemal, Giuseppe Zagotto and Nohad Gresh

J. Chem. Inf. Model., 2022, 62, 6649
DOI: 10.1021/acs.jcim.2c00337