Pyridine Derivatives as Potential Inhibitors for Coronavirus SARS-CoV-2: A Molecular Docking Study

Karthick, Kamaraj; Swarnalatha, K.

doi:10.1177/11779322221146651

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…Moreover, recent studies have shown promising results for the treatment of Coronavirus SARS-CoV-2 using pyridine derivatives. Terpyridine demonstrates potent binding efficacy against the SARS-CoV-2 spike glycoprotein [45], while bis-indolyl pyridines ef- Nitrogen-based heterocyclic chemistry plays a crucial role in small-molecular chemistry, demonstrating remarkable versatility and significance in various biological and pharmacological activities [36][37][38][39]. Specifically, our discovered inhibitors, namely C8 and its analogs (including C10), have a distinctive 1,3,5-triazine backbone and pyridine side of 14 chain.…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, recent studies have shown promising results for the treatment of Coronavirus SARS-CoV-2 using pyridine derivatives. Terpyridine demonstrates potent binding efficacy against the SARS-CoV-2 spike glycoprotein [ 45 ], while bis-indolyl pyridines effectively hinder the infectivity of lentiviral vectors pseudotyped with spike glycoprotein. Further exploration of the interaction between bis-indolyl pyridines and spike RBD uncovered the formation of a hydrogen bond between Gly502 and one of the bis-indolyl pyridine ether groups [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection

Tai,

Yeh,

Chang

et al. 2024

IJMS

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein–ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 μM, 6.7 μM, and 7.6 μM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 μM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 μM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.

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Section: Discussionmentioning

confidence: 88%

“…Moreover, recent studies have shown promising results for the treatment of Coronavirus SARS-CoV-2 using pyridine derivatives. Terpyridine demonstrates potent binding efficacy against the SARS-CoV-2 spike glycoprotein [ 45 ], while bis-indolyl pyridines effectively hinder the infectivity of lentiviral vectors pseudotyped with spike glycoprotein. Further exploration of the interaction between bis-indolyl pyridines and spike RBD uncovered the formation of a hydrogen bond between Gly502 and one of the bis-indolyl pyridine ether groups [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection

Tai,

Yeh,

Chang

et al. 2024

IJMS

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Inhibition of DRP-1 mitochondrial mitophagy and fission by novel α-aminophosphonates bearing pyridine: synthesis, biological evaluations, and computer-aided design

Hekal,

Salem,

El Salam

2024

BMC Chemistry

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Heterocyclic compounds play a crucial role in the drug discovery process and development due to their significant presence and importance. Here, we report a comprehensive analysis of α-aminophosphonates containing pyridine (3a–g), prepared according to a clear-cut, uncomplicated procedure. The phosphonates are thoroughly characterized using various methods, such as elemental analysis, mass spectrometry, proton and carbon NMR, and FT-IR. The molecular docking interactions between the phosphonate and DRP-1 target protein observed that compound 3d had the top-ranked binding energy towards DRP-1 with a value equal to − 9.54 kcal/mol and this theoretically proves its inhibitory efficacy against DRP-1 arbitrated mitochondrial fission. Besides, the anticancer characteristics of compound 3d showed the best IC50 against HepG-2, MCF-7, and Caco-2 which confirmed our results towards suppressing DRP-1 protein (in-silico), and it elucidated no cytotoxic effects against human normal cell line (WI-38). Further, its pharmacokinetics were observed theoretically using ADMET. Moreover,compound 3d investigated the most potent antimicrobial ability against two pathological fungal strains, A. flavus and C. albicans, and four bacterial strains, E. coli, B. subtillis, S. aureus, and P. aregeunosa. Additionally, compound 3d clarified a powerful antioxidant scavenging activity against DPPH and ABTS free radicals (in-vitro). Furthermore, Density functional theory (DFT) was used to study the molecular structures of the synthesized compounds 3a–g, utilizing 6–311++G(d,p) as the basis set and to learn more about the molecules’ reactive sites, the energies of the molecular electrostatic potential (MEP), the lowest unoccupied molecular orbital (LUMO), and the highest occupied molecular orbital (HOMO) were observed. Theoretically, FT-IR and Nuclear magnetic resonance (NMR) measurements are calculated for every compound under investigation to show how theory and experiment relate. It was found that there was an excellent agreement between the theoretical and experimental data. Conclusively, all novel synthesized phosphonates could be used as pharmaceutical agents against pathogenic microbial strains and as anticancer candidates by inhibiting DRP-1-mediated mitochondrial mitophagy.

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Pyridine Derivatives as Potential Inhibitors for Coronavirus SARS-CoV-2: A Molecular Docking Study

Cited by 2 publications

References 52 publications

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection

Inhibition of DRP-1 mitochondrial mitophagy and fission by novel α-aminophosphonates bearing pyridine: synthesis, biological evaluations, and computer-aided design

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