Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors

Botelho, Fernanda D.; Santos, Marcelo C. dos; Gonçalves, Arlan da Silva; Kuča, Kamil; Vališ, Martin; LaPlante, Steven R.; França, Tanos C. C.; Almeida, Joyce S. F. D. de

doi:10.3390/toxins12120746

Cited by 23 publications

(10 citation statements)

References 49 publications

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“…The drugs that showed favorable interactions with all three targets selected in this work were submitted to MVD V R , using the same protocol validated before (Botelho et al, 2020), in order to re-evaluate the protein-ligand interactions using the Moldock Score, a docking algorithm more accurate than PLANTS (Korb et al, 2009). For this task their 3 D structures were constructed in the Spartan 08 software (Hehre et al, 2006), using the semi-empirical method Parametric Method 3 (PM3) (Stewart, 2004) for geometry optimization, and the Natural Population Analysis (NPA) (Reed et al, 1985) method for atomic charges calculations.…”

Section: Docking Studiesmentioning

confidence: 99%

Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets

Almeida

Botelho

Souza

et al. 2021

Journal of Biomolecular Structure and Dynamics

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The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.

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Section: Docking Studiesmentioning

confidence: 99%

Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets

Almeida

Botelho

Souza

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…The negative Gibbs free energy value indicates that the receptor has an attractive interaction with the ligand. Furthermore, the value of the Gibbs free energy of the ligand pair in each conformation is negative, signifying that the receptor with the ligand has a stable bond [49].…”

Section: Molecular Dynamics Resultsmentioning

confidence: 99%

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

2022

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Continuous inflammation can cause new and more severe diseases, thus effective treatments are needed. One of the common inflammation treatments is given by reducing prostaglandins' production through the inhibition of COX-2 activity. This experiment aims to examine the potential application of plant extracts of Adenostemma lavenia and Muntingia calabura (Jamaica cherry) as anti-inflammatory agents in inhibiting COX-2 activity through in silico and in vitro assays. Molecular docking and molecular dynamics simulation were accomplished to evaluate the stability of the complex between COX-2 and ligands. The COX-2 inhibition was determined using the COX-2 Inhibitor Screening Assay KIT. Based on the docking results, the active compound from A. lavenia, ligand 1a,9b-dihydro-1H-cyclopropa[a]anthracene, has the lowest binding energy of -8.7 kcal/mol. In comparison, M. calabura contains 7-hydroxyflavone ligand with a Gibbs free energy of -9.1 kcal/mol. The molecular dynamics study demonstrates that COX-2 maintains its stability when forming interactions with selected compounds from all the tested extracts. The results of the COX-2 inhibition test showed that 96% EtOH extract of A. Lavenia at concentrations of 25 and 100 ppm had an inhibitory activity of 98%; meanwhile, 70% and 96% EtOH extracts of M. calabura at 1000 ppm concentration could inhibit COX-2 activity up to 100%. The results demonstrate that both plants show potential anti-inflammatory activity.

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“…The information about the 3D structures of these proteins retrieved from the Protein Data Bank (PDB) [25] for this study are summarized in Table 1. The software used was Molegro Virtual Docker® (MVD), and the protocol was the same validated before [26,27]. The 3D structures of the ligands were constructed in the Spartan 08 software [28], using the semi-empirical Parametric Method 3 (PM3) [29] for geometry optimization and the Natural Population Analysis (NPA) [30] method for atomic charges calculations.…”

Section: Docking Studiesmentioning

confidence: 99%

Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19

Aghamohammadi

Sirouspour²,

Gonçalves

et al. 2022

J Mol Model

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In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

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Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors

Cited by 23 publications

References 49 publications

Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets

Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19

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