Thiophene-fused γ-lactams inhibit the SARS-CoV-2 main protease via reversible covalent acylation

Gayatri, Lennart Brewitz, Lewis Ibbotson, Eidarus Salah, Shyam Basak, Hani Choudhry and Christopher J. Schofield

Chem. Sci., 2024, 15, 7667
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Asymmetric imidazole-4,5-dicarboxamide derivatives as SARS-CoV-2 main protease inhibitors: design, synthesis and biological evaluation

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C6-Alkoxy substituted penicillins are potent non-covalently binding inhibitors of the SARS-CoV-2 main protease

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Phytonutrient formulation using gum Arabic and Adansonia Digitata pulp: Lessons for boosting the human immune system - part 1

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Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies

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European Journal of Medicinal Chemistry, 2025, 291, 117603
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Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 Mpro

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From ML300 to Novel Non-covalent Inhibitors of SARS‑CoV‑2 Main Protease via Evolutionary De Novo Design, Virtual Screening, Molecular Dynamics, and Retrosynthetic Strategies

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Identification of lead small molecules for the design and development of potent severe acute respiratory syndrome coronavirus 2 main protease inhibitors

Elvis Awuni

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Noncovalent Inhibitors of SARS-CoV-2 Main Protease: A Rescaffolding Attempt

Tim Krischuns, Sylvain Paisant, Kuang-Yu Chen, Laura N. Thirion, Agnès Zettor, Jeanne Chiaravalli, Yves Jacob, Marco Bellinzoni, Nadia Naffakh and Yves L. Janin

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Structure-Based Design of Covalent SARS-CoV-2 Main Protease Inhibitors Targeting the Nirmatrelvir-Resistant E166 Mutants

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JACS Au, 2026, 6, 233
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Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants

Xu Wang, Dimitar Gotchev, Kristi Yi Fan, Marvin M. Vega, Nagraj Mani, Kayleigh McGovern-Gooch, Andrea Cuconati, Breanna Tercero, Xiaohe Wang, Philip Carpino, Klaus Maskos, Paolo A. Centrella, Andreas Schmitt, Franziska Preuss, Archna Prasad, Chia-yi Chen, Matthew A. Clark, John P. Guilinger, Shawn Johnstone, Konstanze von König, Anthony D. Keefe, Jenny Liu, Stéphane Turcotte, Ying Zhang, Debora L. Konz Makino, Angela M. Lam, Andrew G. Cole and Michael J. Sofia

J. Med. Chem., 2024, 67, 19623
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Fixing the Achilles Heel of Pfizer’s Paxlovid for COVID-19 Treatment

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Development of Orally Bioavailable Octahydroindole-Based Peptidomimetic Derivative as a Broad-Spectrum Inhibitor against HCoV-OC43 and SARS-CoV-2

Shulei Hu, Yumin Zhang, Chenchen Wang, Jian Li, Haixia Su, Xiong Xie, Jiang Wang, Jinlin Wang, Junyuan Cao, Xiaofei He, Yechun Xu, Leike Zhang, Wenhao Dai and Hong Liu

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Process Development of Key α‐Hydroxyamide Intermediate WUT‐8 (Multikilogram Scale) for the Synthesis of Anti‐COVID‐19 Drug “Leritrelvir”

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Engineering GFP–NanoLuc fusion substrates for sensitive, quantitative detection of protease activity via BRET

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Ensitrelvir suppresses prolonged olfactory abnormalities derived from SARS-CoV-2 infection in hamsters

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Structure-guided discovery of a small molecule inhibitor of SARS-CoV-2 main protease with potent in vitro and in vivo antiviral activities

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Discovery of peptidomimetic spiropyrrolidine derivatives as novel 3CLpro inhibitors against SARS-CoV -2

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Discovery of an Orally Bioavailable Reversible Covalent SARS-CoV-2 Mpro Inhibitor with Pan-Coronavirus Activity

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Chromene-Thiazole Derivatives as Potential SARS-CoV-2 Mpro Inhibitors: Synthesis and Computational Studies

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Crystal structures of coronaviral main proteases in complex with the non-covalent inhibitor X77

Haihai Jiang, Wenwen Li, Xuelan Zhou, Jin Zhang and Jian Li

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In Silico Development of SARS-CoV-2 Non-Covalent Mpro Inhibitors: A Review

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Direct‐to‐Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery

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Beyond Antiviral Therapy: Untapped Potential of HIV & HCV Protease Inhibitors

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An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations

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Influence of Steric and Electronic Properties of P2 Groups on Covalent Inhibitor Binding to SARS-CoV-2 Main Protease

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Overview of recent strategic advances in antiviral covalent inhibitors

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Trends in covalent drug discovery: a 2020–23 patent landscape analysis focused on select covalent reacting groups (CRGs) found in FDA-approved drugs

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Naphthalen-1-ylethanamine–containing small molecule inhibitors of the papain-like protease of SARS-CoV-2

Kouki Shinohara, Takuya Kobayakawa, Kohei Tsuji, Yuki Takamatsu, Hiroaki Mitsuya and Hirokazu Tamamura

European Journal of Medicinal Chemistry, 2024, 280, 116963
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A magnetic bead-based fluorescent substrate for sensitive assay of SARS-CoV-2 3C-like protease activity

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A patent review of Mpro protease inhibitors for the treatment of COVID-19 infections (2020 – present)

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Effects of SARS-CoV-2 Main Protease Mutations at Positions L50, E166, and L167 Rendering Resistance to Covalent and Noncovalent Inhibitors

Andrey Kovalevsky, Annie Aniana, Rodolfo Ghirlando, Leighton Coates, Victoria N. Drago, Lauren Wear, Oksana Gerlits, Nashaat T. Nashed and John M. Louis

J. Med. Chem., 2024, 67, 18478
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SARS-CoV-2 Papain-Like Protease Inhibitors Based on Naphthalen-1-ylethanamine and Halogenated Benzene Moieties

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ACS Omega, 2025, 10, 47165
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