Design, synthesis and biological evaluation of peptidomimetic benzothiazolyl ketones as 3CLpro inhibitors against SARS-CoV-2

You, M. James; X.-O., Shu,; Zhen, Jianyu; Zhu, Mengwei; Fu, Tong; Zhang, Yan; Jiang, Xiangrui; Zhang, Leike; Xu, Yechun; Zhang, Y; Zhang, Qiumeng; Shen, Jingshan

doi:10.1016/j.ejmech.2023.115512

Cited by 3 publications

(4 citation statements)

References 45 publications

(50 reference statements)

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“…The simpler azabicyclo[2.2.1]heptane ring system has also been introduced in the structure of such inhibitors. 310 Further insights were provided in the course of an extensive study of boceprevir analogues which reported some key elements to achieve an antiviral effect in cellulo . 311 Moreover, the same research group recently reported the azaspiro[4.4]nonane derivative MPI-60 ( 82 ), which displays promising antiviral properties 312 and a structure of SARS-CoV-2 M pro bound to this compound was obtained ().…”

Section: Inhibitors Of the Sars-cov-2 Main Proteasementioning

confidence: 99%

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

Janin

2024

RSC Med. Chem.

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Section: Inhibitors Of the Sars-cov-2 Main Proteasementioning

confidence: 99%

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

Janin

2024

RSC Med. Chem.

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“…CoV-2 M pro inhibitors, which were designed starting from Nirmatrelvir [63]. They firstly introduced the [2.2.1]azabicylic ring at the P2 position and the benzothiazolyl warhead at the C-terminus; then, they began to explore different substitutions at P3.…”

Section: Yang Et Al Reported Novel Benzothiazolyl-based Peptidomimeti...mentioning

confidence: 99%

“…Compound 48 exhibited an interesting inhibitory activity against SARS-CoV-2 M pro (IC 50 = 1.65 µM), a good antiviral activity against SARS-CoV-2-infected VeroE6 cells (EC 50 = 0.18 µM) and low cytotoxicity. Most importantly, the PK properties and target selectivity of compound 48 were superior to those of other derivatives [63]. In the already mentioned work of Kneller et al, besides the development of nitrilebased compounds, the authors designed a novel SARS-CoV-2 M pro inhibitor bearing a benzothiazolyl ketone warhead [35].…”

Section: Yang Et Al Reported Novel Benzothiazolyl-based Peptidomimeti...mentioning

confidence: 99%

“…Other quinazolin-4-one-based non-covalent inhibitors of SARS-CoV-2 M pro are compounds 160 and 161 (Figure 79A), proposed by Zhang et al [116], which were developed starting from the lead Baicalein (159 in Figure 79A) by replacing its chromen-4-one ring and varying the substitution pattern in C2 and N3 positions. The most interesting compound (160) contains a phenyl group both at the C2 and N3 position and posseses higher activity as compared to Baicalein [63]. Furthermore, 160 and 161 showed optimal selectivity against other human proteases and low cytotoxicity [116].…”

Section: Non-covalent Inhibitorsmentioning

confidence: 99%

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Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Citarella,

Dimasi,

Moi

et al. 2023

Biomolecules

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The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

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Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2

Yan,

Liu,

et al. 2024

Future Medicinal Chemistry

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Background: The epidemic caused by SARS-CoV-2 swept the world in 2019. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in viral replication, and its inhibition could inhibit viral replication. Materials & methods: The virtual screen based on receptor–ligand pharmacophore models and molecular docking were conducted to obtain the novel scaffolds of the 3CLpro. The molecular dynamics simulation was also carried out. All compounds were synthesized and evaluated in biochemical assays. Results: The compound C2 could inhibit 3CLpro with a 72% inhibitory rate at 10 μM. The covalent docking showed that C2 could form a covalent bond with the Cys145 in 3CLpro. Conclusion: C2 could be a potent lead compound of 3CLpro inhibitors against SARS-CoV-2.

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Design, synthesis and biological evaluation of peptidomimetic benzothiazolyl ketones as 3CLpro inhibitors against SARS-CoV-2

Cited by 3 publications

References 45 publications

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

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

Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2

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