Triagem Virtual Inversa Como Ferramenta Para a Química De Produtos Naturais

Carregal, Ana Paula; Taranto, Alex Gutterres; Comar, Moacyr; Lima, Luciana Alves Rodrigues dos Santos; Siqueira, João Máximo de

doi:10.5216/ref.v8i1.10561

Cited by 3 publications

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“…The compounds shown in Figure 1A were submitted to a search by the IVS program called sc‐PDB,18, 19 as described previously,20 against the molecular targets deposited in the PDB. Then, with the IVS results, the molecular docking method was performed to fit the ligand into the active site of the target proteins.…”

Section: Methodsmentioning

confidence: 99%

Inverse virtual screening studies of selected natural compounds from cerrado

Carregal

Comar

Alves

et al. 2012

Int J of Quantum Chemistry

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Several medicinal plants have been studied in recent years in Brazil. However, despite many efforts, the pharmacological mechanisms of many natural products are still unknown. Several biological assays in vivo and in vitro are needed to further address this issue, which increases the cost of these studies. The main goal of this study was to apply the methodology of inverse virtual screening (IVS), followed by docking studies, and refinement by molecular dynamics (MD) simulation and quantum mechanical/molecular mechanical to determine the pharmacological receptors for five selected natural products with the exception of the benzoxazinone isolated from the exudate of the radicle of the crop species which were mainly isolated from the Cerrado species, obtained from Cerrado, a typical Brazilian biome. Initially, the structures of the natural compounds were generated using the online software program sc-PDB, which searches for molecular targets deposited in the protein data bank. The ligands were docked against target proteins found in IVS stepforming complexes, which were refined again using MD simulations by ff03 force field for 1 ns. Finally, the binding energy for each complex was obtained by the ONIOM (PM6:UFF) method. As a result, these calculations suggested possible molecular targets for these natural compounds. Among the targets found were 1EH4, 2A4Z, 1H49, 1JT2, 2BNJ, and 3FW9, which are involved in cancer and rheumatoid arthritis pathologies, indicating that they are promising molecular targets. In this study, we proposed a biological assay for these natural compounds. The results indicate that structural changes may be proposed to generate compounds that are able to bind more strongly to the receptor and become new drug candidates, thus optimizing the search for lead natural compounds.

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Section: Methodsmentioning

confidence: 99%

Inverse virtual screening studies of selected natural compounds from cerrado

Carregal

Comar

Alves

et al. 2012

Int J of Quantum Chemistry

Self Cite

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“…A TVI é constituída por um banco de dados com estruturas proteicas, de grande importância farmacológica, se fundamentando em ensaios in sílico, sendo os receptores farmacológicos os que possuem atuação para determinado ligante de interesse. Seu objetivo principal é identificar os compostos de uma biblioteca que tenham maior probabilidade de se ligar a um alvo biológico, possibilitando realizar uma previsão da bioatividade da molécula consultada (CARREGAL et al, 2011;RODRIGUES, 2012).…”

Section: Introductionunclassified

Uso De Mikania Glomerata E Curcuma L Como Potencial Inibidor Da Protease Covid-19 No Manejo Dos Sintomas Por Estudo De Docking Molecular

Carvalho¹,

Pereira²,

Santos³

2023

RECIMA21

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A doença COVID-19, causada pelo SARS-CoV-2, conhecida como coronavírus da síndrome respiratória, foi considerada uma pandemia no ano de 2020, e continua sendo um dos grandes desafios da atualidade, pois até então, não se tem um tratamento específico. Os fitoterápicos têm sido utilizados como adjuvantes nos sintomas da COVID-19 em algumas regiões. Este trabalho teve como objetivo verificar a eficácia dos compostos presentes na Mikania glomerata e no Curcuma longa para tratamento dos sintomas da COVID-19, utilizando a Triagem Virtual Inversa para identificar os compostos e definir as proteases mais prevalentes na COVID-19, a fim de determinar quais são os compostos mais efetivos. Trata-se de uma pesquisa exploratória, do tipo descritiva, com características qualitativa e quantitativa. As pesquisas foram realizadas no banco de dados do programa computacional RCSB Protein Data Bank, através da triagem virtual. A escolha de tais plantas ocorreu devido a sua potencial atividade farmacológica contra os principais sintomas presentes na doença da COVID-19. Foi possível observar que a maioria dos compostos analisados, apresentaram um coeficiente de tanimoto igual a 1, tendo uma maior compatibilidade com as moléculas da COVID-19, possibilitando sua utilização para produção de uma futura terapia medicamentosa.

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“…As a result, docking is able to rank the ligands through electrostatic and van der Waals forces. 20,22 Currently, this methodology is considered to be a high performance tool to search for an appropriate ligand in a set of thousands of compounds (virtual screening, VS) 34 or to find a molecular template for a specific ligand (inverse virtual screening). 35 Such docking simulations can be performed using rigid or flexible approaches.…”

Section: Introductionmentioning

confidence: 99%

Docking and QM/MM Studies of NS2B-NS3pro Inhibitors: a Molecular Target against the Dengue Virus

Godói¹,

Lima²,

Comar³

et al. 2016

J. Braz. Chem. Soc.

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Dengue virus (DENV) has been characterized as having great clinical importance in the world, as there is no specific treatment against this virus. The NS2B-NS3pro complex is essential for the replication and maturation of DENV and is a potential pharmacological target. The present study aims to evaluate and understand the interactions and affinities (via molecular docking/AutoDock Vina) of 16 peptidomimetic derivatives applied to a NS2B-NS3pro DENV-2 complex constructed by homology modeling (via SWISS-MODEL). Two compounds were selected as potential inhibitors of this protein complex. In addition, these compounds possess important interactions involving Ser135, Gly169 and Tyr161, which have been described previously to be fundamental to the recognition of inhibitors directed to this receptor. Thus, the involvement of these residues is significant pharmacologically because they may contribute to the inhibitory action of this molecular target against DENV.Keywords: dengue, inhibitors, NS2B-NS3pro, molecular modeling IntroductionDengue fever affects approximately 390 million people annually, with higher prevalence in tropical and subtropical regions.1 Dengue virus (DENV) belongs to the genus Flavivirus and Flaviviridae families and is transmitted by the bite from female mosquitoes of the genus Aedes and species A. albopictus and A. aegypti.2 Currently, there is no specific therapy available against DENV; however, palliative treatments to circumvent symptoms caused by the disease are available. DENV has four antigenically distinct serotypes (i.e., DENV1-4), which makes it difficult to develop an effective vaccine. 2-4The viral RNA encodes 10,173 nucleotides that are translated into a polyprotein. This protein is then cleaved by viral and cellular proteases, culminating in the release of three structural proteins (i.e., capsid (C), precursor membrane protein (prM) and envelope (E)) and seven nonstructural proteins (i.e., NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). 2,5 The serine protease called NS2B-NS3pro DENV has considerable genetic similarity with the analogous West Nile virus (WNV) protease. 6 This protease complex is directly related to replication and maturation of the virus, and it thus represents a promising molecular template for the treatment of these two pathogens. [5][6][7] The N-terminal region of NS2B-NS3pro has 187 amino acids and the catalytic triad His51-Asp75-Ser135 constitutes the active domain of the serine protease, which is essential for cleavage of the viral polyprotein. 6,8 Its catalytic mechanism involves the nucleophilic attack of the oxygen from the serine hydroxyl group and the electrophilic carbon of the peptide bond to be cleaved. 6,[9][10][11] Erbel et al. 6 identified important residues for inhibitor recognition in NS3pro such as Gly151, Gly153 and Tyr161. Regarding the organization of the flaviviral active site, Aleshin et al. 12 demonstrated that a precise spatial arrangement is required to enhance the nucleophilicity of the serine hydroxyl group present in the His-Asp-Ser catalytic t...

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Triagem Virtual Inversa Como Ferramenta Para a Química De Produtos Naturais

Cited by 3 publications

References 0 publications

Inverse virtual screening studies of selected natural compounds from cerrado

Inverse virtual screening studies of selected natural compounds from cerrado

Uso De Mikania Glomerata E Curcuma L Como Potencial Inibidor Da Protease Covid-19 No Manejo Dos Sintomas Por Estudo De Docking Molecular

Docking and QM/MM Studies of NS2B-NS3pro Inhibitors: a Molecular Target against the Dengue Virus

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