Triazole, imidazole, and thiazole-based compounds as potential agents against coronavirus

Seck, I; Nguemo, Filomain

doi:10.1016/j.rechem.2021.100132

Cited by 28 publications

(19 citation statements)

References 83 publications

(80 reference statements)

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“…In earlier studies, the 1,2,3-triazole scaffolds were identified to possess antiviral, anti-inflammatory, antibacterial, and anti-cancerous properties [ [18] , [19] , [20] , [21] ]. In addition, the 1,2,3-triazole scaffolds were also shown to have an antiviral effect on the M pro in experimental studies [ [22] , [23] , [24] ]. Based on the above-information, we aimed to identify the M pro inhibitors with high-affinity binding and stability from our selected molecules in comparison to co-crystallized inhibitors by employing molecular dynamics (MD) and enhanced sampling simulations.…”

Section: Introductionmentioning

confidence: 99%

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations

Singh

Bhardwaj

Das

et al. 2022

Computers in Biology and Medicine

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Section: Introductionmentioning

confidence: 99%

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations

Singh

Bhardwaj

Das

et al. 2022

Computers in Biology and Medicine

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“…41 , 42 Most recently, thiazole-based inhibitors have been reported for SARS-CoV-2. 43 , 44 Synthetic indazole-based compounds have exhibited function as anti-inflammatory, antiarrhythmic, antitumor, antifungal, antibacterial, and anti-HIV drugs. [ 45 ] Indazole-based drugs are also being considered as SARS-CoV-2 M Pro inhibitors.…”

Section: Introductionmentioning

confidence: 99%

“…Thiazole-based compounds have shown promise as SARS-CoV M Pro inhibitors with best-in-class compounds demonstrating K I values of 2.2 μM and IC 50 as low as 3 μM. 43 , 44 A machine learning approach to identifying investigational or off-market drug targets for SARS-CoV-2 identified an indazole containing compound as one of the most promising with an estimated binding affinity of -9 kcal/mol. [ 46 ] Given the wide-ranging and beneficial pharmacological impacts of thiazole- and indazole-containing compounds, and the community’s interest in these drugs as potential SARS-CoV-2 M Pro inhibitors, we seek to elucidate the usefulness of thiazolyl-indazole derivatives as potential scaffolds for further pharmaceutical development and exploration.…”

Section: Introductionmentioning

confidence: 99%

“…[ 46 ] Given the wide-ranging and beneficial pharmacological impacts of thiazole- and indazole-containing compounds, and the community’s interest in these drugs as potential SARS-CoV-2 M Pro inhibitors, we seek to elucidate the usefulness of thiazolyl-indazole derivatives as potential scaffolds for further pharmaceutical development and exploration. [41] , [42] , [43] , [44] , [45] , [46] , 48 …”

Section: Introductionmentioning

confidence: 99%

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Investigating novel thiazolyl-indazole derivatives as scaffolds for SARS-CoV-2 MPro inhibitors

Airas

Bayas

Ousidi

et al. 2022

European Journal of Medicinal Chemistry Reports

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COVID-19 is a global pandemic caused by infection with the SARS-CoV-2 virus. Remdesivir, a SARS-CoV-2 RNA polymerase inhibitor, is the only drug to have received widespread approval for treatment of COVID-19. The SARS-CoV-2 main protease enzyme (M Pro ), essential for viral replication and transcription, remains an active target in the search for new treatments. In this study, the ability of novel thiazolyl-indazole derivatives to inhibit M Pro is evaluated. These compounds were synthesized via the heterocyclization of phenacyl bromide with ( R )-carvone, ( R )-pulegone and ( R )-menthone thiosemicarbazones. The binding affinity and binding interactions of each compound were evaluated through Schrödinger Glide docking, AMBER molecular dynamics simulations, and MM-GBSA free energy estimation, and these results were compared with similar calculations of M Pro binding various 5-mer substrates (VKLQA, VKLQS, VKLQG) and a previously identified M Pro tight-binder X77. From these simulations, we can see that binding is driven by residue specific interactions such as π-stacking with His41, and S/π interactions with Met49 and Met165. The compounds were also experimentally evaluated in a M Pro biochemical assay and the most potent compound containing a phenylthiazole moiety inhibited protease activity with an IC 50 of 92.9 μM. This suggests that the phenylthiazole scaffold is a promising candidate for the development of future M Pro inhibitors.

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“…Moreover, owing to the nature of their chemical properties, this group of ligands can be easily synthesized [19][20][21]. The triazole group-based ligands could be a potential drug-candidate for use against the SARS-CoV-2 virus [22,23]. Efforts to develop efficient therapeutic strategies against COVID-19 are still in progress.…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

2021

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The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies.

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Triazole, imidazole, and thiazole-based compounds as potential agents against coronavirus

Cited by 28 publications

References 83 publications

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations

Investigating novel thiazolyl-indazole derivatives as scaffolds for SARS-CoV-2 MPro inhibitors

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

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