The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022

Pang, Xiaowu; Xu, Wei; Liu, Yang; Li, Hua; Chen, Lixia

doi:10.1016/j.ejmech.2023.115491

Cited by 48 publications

(17 citation statements)

References 104 publications

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“…Many reports have already listed all the, sometimes related, 36 inhibitors reported for their effect on chymotrypsin-like proteases of human rhinovirus, 37–40 enterovirus 71, 41 SARS and MERS coronaviruses 42–46 and then SARS-CoV-2. 2–4,6,17,18,47–70 In the present text, the many publications 26 solely based on in silico docking approaches 71,72 and/or on traditional/ancestral medicine beliefs which only described frequent hitters/pan-assay interference compounds (PAINS) 73–77 were ignored. This choice is a bid to discourage such all too obvious pollution of the scientific literature, 78,79 not to mention the issue of lack of reproducibility of some data from the academia.…”

Section: Introductionmentioning

confidence: 99%

On the origins of SARS-CoV-2 main protease inhibitors

Janin

2024

RSC Med. Chem.

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Section: Introductionmentioning

confidence: 99%

On the origins of SARS-CoV-2 main protease inhibitors

Janin

2024

RSC Med. Chem.

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“…Additionally, several inhibitors of 3CL pro and other targets are undergoing clinical trials (Mukae et al, 2022;Lei et al, 2022). Many of these inhibitors emerged through repurposing, for example of inhibitors of proteases (Pang et al, 2023). In contrast, fragment screening and FBDD inherently aim at identifying novel starting points.…”

Section: Introductionmentioning

confidence: 99%

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket

Huang,

Metz,

Lange

et al. 2024

Acta Crystallogr D Struct Biol

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To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin-based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography.

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“…The properties of Mpro inhibitor predominantly hinges on the interaction between the drugs and protease. [9,10] Mpro, a serine protease, is instrumental in the maturation of viral particles. Its active site comprises two cysteine residues, to which drugs typically bind, either singly or in unison, thereby inhibiting the activity of Mpro.…”

Section: Introductionmentioning

confidence: 99%

“…The properties of Mpro inhibitor predominantly hinges on the interaction between the drugs and protease [9,10] . Mpro, a serine protease, is instrumental in the maturation of viral particles.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Efficacy of Noncovalent SARS‐CoV‐2 Main Protease Inhibitors: A Computational Simulation Analysis Study

Xiong,

Zhang,

Jiang

et al. 2024

Chemistry & Biodiversity

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The SARS‐CoV‐2 main protease, as a key target for antiviral therapeutics, is instrumental in maintaining virus stability, facilitating translation, and enabling the virus to evade innate immunity. Our research focused on designing non‐covalent inhibitors to counteract the action of this protease. Utilizing a 3D‐QSAR model and contour map, we successfully engineered eight novel non‐covalent inhibitors. Further evaluation and comparison of these novel compounds through methodologies including molecular docking, ADMET analysis, frontier molecular orbital studies, molecular dynamics simulations, and binding free energy revealed that the inhibitors N02 and N03 demonstrated superior research performance (N02 ΔGbind = ‐206.648 kJ/mol, N03 ΔGbind = ‐185.602 kJ/mol). These findings offer insightful guidance for the further refinement of molecular structures and the development of more efficacious inhibitors. Consequently, future investigations can draw upon these findings to unearth more potent inhibitors, thereby amplifying their impact in the treatment and prevention of associated diseases.

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The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022

Cited by 48 publications

References 104 publications

On the origins of SARS-CoV-2 main protease inhibitors

On the origins of SARS-CoV-2 main protease inhibitors

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket

Exploring the Efficacy of Noncovalent SARS‐CoV‐2 Main Protease Inhibitors: A Computational Simulation Analysis Study

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