A Drug Repurposing Approach for Antimalarials Interfering with SARS-CoV-2 Spike Protein Receptor Binding Domain (RBD) and Human Angiotensin-Converting Enzyme 2 (ACE2)

Coghi, Paolo; Yang, Li; Ng, Jerome P. L.; Haynes, Richard K.; Memo, Maurizio; Gianoncelli, Alessandra; Wong, Vincent Kam Wai; Ribaudo, Giovanni

doi:10.3390/ph14100954

Cited by 18 publications

(23 citation statements)

References 64 publications

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“…R f (CH 2 Cl 2 ) 0.5; δ H (600 MHz, CDCl 3 ) 8.82 (1H, d, J = 4.9 Hz, H-2), 8.09 (1H, d, J = 2.4 Hz, H-8), 8.01 (1H, d, J 9.3, H-5), 7.49 (1H, dd, J 2.4 and 9.3, H-6) 7.12 (1H, d, J 4.9, H-3) ppm; δ C (150 MHz, CDCl 3 ) 150.9, 149.1, 146.8, 136.9, 127.9, 123.8, 119.9, 108.7 ppm. The spectral characteristics are consistent with those of 2 in the literature [20].…”

Section: Chemistrysupporting

confidence: 89%

“…BLI also provides the calculation of kinetic parameters, such as association rate (k on ) and dissociation rate (k dis ), as well as of dissociation constant (K D ). This technique was recently adopted to screen RBD ligands in combination with virtual screening [20]. As shown in Figure S11 of the Supplementary Materials, the results of BLI conducted on synthesized compound demonstrated a poor affinity with RBD spike of SARS-CoV-2 (delta variant), with a modest correlation value.…”

Section: Resultsmentioning

confidence: 99%

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2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

Yun

Xie

et al. 2022

Molbank

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The 1,2,3-triazole ring system can be easily obtained by copper-catalyzed click reaction of azides with alkynes. 1,2,3-Triazole exhibits a myriad of biological activities, including antimalarial, antibacterial, and antiviral activities. We herein reported the synthesis of quinoline-based [1,2,3]-triazole hybrid via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of 2-bromobenzaldehyde. The compound was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), ultraviolet (UV), and high-resolution mass spectroscopies (HRMS). This compound was screened in vitro against two different normal cell lines. Preliminary studies attempted to evaluate its interaction with Delta RBD of spike protein of SARS-CoV-2 by bio-layer interferometry. Finally, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties.

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Section: Chemistrysupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

Yun

Xie

et al. 2022

Molbank

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“…(2020) demonstrated that withanone efficiently inhibited the interaction between ACE2R and RBD in vitro , with an IC 50 of 0.33 ng/mL [ 62 ]. Two other compounds structurally close to withanolide F, peimine and artemisone, also exhibited similar activities [ 64 , 65 ]. In a study by Wang et al, Peimine inhibited variants of SARS‐CoV‐2 infection in furin‐overexpressing cells with an IC 50 of 0.4 μM against wild-type, alpha, and beta variants.…”

Section: Resultsmentioning

confidence: 99%

Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern

Chinnadurai¹,

Ponne

Loganathan

et al. 2022

Mol Divers

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Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) pathogenesis is initiated by the binding of SARS-CoV-2 spike (S) protein with the angiotensin-converting enzyme 2 receptor (ACE2R) on the host cell surface. The receptor-binding domain (RBD) of the S protein mediates the binding and is more prone to mutations resulting in the generation of different variants. Recently, molecules with the potential to inhibit the interaction of S protein with ACE2R have been of interest due to their therapeutic value. In this context, the present work was performed to identify potential RBD binders from the Indian medicinal plant's phytochemical database through virtual screening, molecular docking, and molecular dynamic simulation. Briefly, 1578 compounds filtered from 9596 phytochemicals were chosen for screening against the RBD of the native SARS-CoV-2 S protein. Based on the binding energy, the top 30 compounds were selected and re-docked individually against the native and five variants of concern (VOCs: alpha, beta, gamma, delta, and omicron) of SARS-CoV-2. Four phytochemicals, namely withanolide F, serotobenine, orobanchol, and gibberellin A51, were found to be potential RBD binders in native and all SARS-CoV-2 VOCs. Among the four, withanolide F exhibited lower binding energy (− 10.84 to − 8.56 kcal/mol) and better ligand efficiency (− 0.3 to − 0.25) against all forms of RBD and hence was subjected to a 100 ns MD simulation which confirmed its stringent binding to the RBDs in native and VOCs. The study prioritizes withanolide F as a prospective COVID-19 (Coronavirus disease) therapeutic agent based on the observations. It warrants deeper investigations into the four promising leads for understanding their precise therapeutic value. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10580-9.

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“…Molavi et al repurposed 1760 FDA-approved drugs to Mpro and RdRp, and Rajpoot et al repurposed 291 drugs to Mpro and PLpro. More similar works include refs , , , , , , , , , , and − .…”

Section: Methods and Approachesmentioning

confidence: 97%

“… 1146 repurposed 291 drugs to Mpro and PLpro. More similar works include refs ( 599 , 609 , 622 , 624 , 628 , 632 , 637 , 838 , 875 , 889 , and 1147 − 1173 ).…”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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A Drug Repurposing Approach for Antimalarials Interfering with SARS-CoV-2 Spike Protein Receptor Binding Domain (RBD) and Human Angiotensin-Converting Enzyme 2 (ACE2)

Cited by 18 publications

References 64 publications

2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde

Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

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