In silico investigation to select the most fitting mTOR inhibitors using AutoDock Vina Oral Granule

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

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In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

10.26434/chemrxiv.12952115.v1 ◽

2020 ◽

Author(s):

Rafael Blasco ◽

Julio Coll

Keyword(s):

In Silico ◽

Chemical Properties ◽

Structural Similarity ◽

Binding Pocket ◽

Binding Affinities ◽

Structural Protein ◽

Autodock Vina ◽

Natural Ligands ◽

Final Optimization

<p>The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further <i>in silico</i> predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.</p>

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An in silico protocol for identifying mTOR inhibitors from natural products

Molecular Diversity ◽

10.1007/s11030-014-9543-5 ◽

2014 ◽

Vol 18 (4) ◽

pp. 841-852 ◽

Cited By ~ 5

Author(s):

Lei Chen ◽

Ling Wang ◽

Qiong Gu ◽

Jun Xu

Keyword(s):

Natural Products ◽

In Silico ◽

Mtor Inhibitors

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Potential natural mTOR inhibitors screened by in silico approach and suppress hepatic stellate cells activation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2017.1411295 ◽

2017 ◽

Vol 36 (16) ◽

pp. 4220-4234 ◽

Cited By ~ 8

Author(s):

Varadharajan Thiyagarajan ◽

Kuan-Wei Lee ◽

Max K. Leong ◽

Ching-Feng Weng

Keyword(s):

Hepatic Stellate Cells ◽

In Silico ◽

Mtor Inhibitors ◽

Stellate Cells

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Studi In Silico, Sintesis, dan Uji Sitotoksik Senyawa P-Metoksi Kalkon terhadap Sel Kanker Payudara MCF-7

Jurnal Sains Farmasi & Klinis ◽

10.25077/jsfk.6.3.243-249.2019 ◽

2019 ◽

Vol 6 (3) ◽

pp. 243

Author(s):

Rahma Dona ◽

Neni Frimayanti ◽

Ihsan Ikhtiarudin ◽

Benni Iskandar ◽

Fikri Maulana ◽

...

Keyword(s):

In Silico ◽

Van Der Waals ◽

Autodock Vina ◽

Mcf 7

Kalkon (1,3-difenil-2-propene-1-on) adalah salah satu senyawa golongan flavonoid yang memiliki beragam aktivitas biologis diantaranya sebagai antikanker. Penelitian ini bertujuan untuk mengetahui efek sitotoksik analog kalkon (E)-3-(4-metoksifenil)-1-fenilprop-2-en-1-on dengan menggunakan teknik komputerisasi (docking), senyawa analog kalkon tersebut disintesis menggunakan reaksi kondensasi Claisen-Schmidt dengan katalis basa secara metode iradiasi gelombang mikro. Studi in silico ini dilakukan antara senyawa kalkon dengan protein dengan kode PDB ID P521 dengan menggunakan program AutoDock Vina, sedangkan uji aktivitas sitotoksik senyawa kalkon dilakukan terhadap sel kanker payudara MCF-7 menggunakan metode WST-8. Berdasarkan hasil docking, senyawa kalkon (E)-3-(4-metoksifenil)-1-fenilprop-2-en-1-on memiliki potensi sebagai penghambat aktif terhadap sel kanker payudara MCF-7 ditandai dengan senyawa ini memiliki nilai energi bebas ikatan yang lebih kecil dibandingkan doxorubicin sebagai pembanding; memiliki 4 persamaan asam amino dengan doxorubicin dimana interaksi yang terbentuk terdiri dari 4 jenis ikatan yaitu ikatan hidrogen, ikatan van der Waals, ikatan pi-sigma dan ikatan pi –alkil. Dari hasil uji sitotoksik antara sel kanker MCF-7 dan senyawa kalkon diperoleh nilai IC50 sebesar 48,18 µg/mL. Dari penelitian tersebut dapat disimpulkan bahwa senyawa analog kalkon (E)-3-(4-metoksifenil)-1-fenilprop-2-en-1-on dapat berpotensi sebagai inhibitor terhadap sel kanker payudara MCF-7

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Analysis Docking Of Plasmodium Falciparum Enoyl Acyl Carrier Protein Reductase (Pfenr) With Organic Compunds From Virtual Screening Of Herbal Database

Acta Chimica Asiana ◽

10.29303/aca.v3i1.14 ◽

2020 ◽

Vol 3 (1) ◽

pp. 127

Author(s):

Nya Daniaty Malau ◽

St Fatimah Azzahra

Keyword(s):

Plasmodium Falciparum ◽

Virtual Screening ◽

In Silico ◽

Fatty Acid Biosynthesis ◽

Acyl Carrier Protein ◽

Chemotherapeutic Agents ◽

Effective Vaccine ◽

Carrier Protein ◽

Autodock Vina ◽

In Silico Screening

Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silico screening, or also known as virtual screening. One of enzyme target that important for growth of the malaria parasite is Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type II will be terminated. In this research, in silico screening was performed using AUTODOCK VINA software to find inhibitor candidates of PfENR by using ligands from the database of Medicinal Plants in Indonesia. On the AUTODOCK VINA software moleculer docking experiments were performed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors.

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PREDIÇÃO FÍSICO-QUÍMICA, MODELAGEM E ANÁLISE DO MECANISMO DE INTERAÇÃO DA QUITINASE Mo-chi1 [Moringa oleifera, LAM.], COM POLI-β-(1-4)-N-ACETIL-D-GLUCOSAMINE: UMA ABORDAGEM in silico

DESAFIOS Revista Interdisciplinar da Universidade Federal do Tocantins ◽

10.20873/uft.2359-3652.2018vol5n1p111 ◽

2018 ◽

Vol 5 (1) ◽

pp. 111-120

Author(s):

Lara Cristhian Costa Bezerra ◽

Evaristo Wagner Alves de Queiroz ◽

José Ednésio da Cruz Freire

Keyword(s):

In Silico ◽

Moringa Oleifera ◽

Plant Genome ◽

Autodock Vina ◽

Genome Database ◽

Chinese Herbal ◽

Α Helix ◽

Herbal Plant ◽

Moringa Oleifera Lam

Quitinases são enzimas capazes de hidrolisar ligações β-(1,4) entre os resíduos de N-acetil-β-D-glucosamina (GlcNAc), presente em diversos organismos. Elucidar as propriedades físico-químicas da Mo-chi1 identificada na planta Moringa oleifera empregando ferramentas in silico. Após busca no Chinese Herbal Plant Genome Database, a sequência (ID: 10006495) foi analisada quanto ao peptídeo sinal, propriedades físico-químicas, pontes de sulfeto, domínios, estruturas secundárias, modelagem. O modo de interação entre Mo-chi1 e quitina foi predito com o programa AutoDock Vina. A Mo-chi1 possui peptídeo sinal com 19 aminoácidos de comprimento (clivado: Ala19 e Ile20), formando polipeptídio maduro de 379 resíduos. A madura possui Mr = 39,56 kDa, pI = 5.44, II = 35.61 e GRAVY = -0.135. Possui uma ponte de sulfeto (5Cys-Cys398). Pertencer à família das GH18 com E-value de 7.43e-153 (CDD) e de 2.3e-90 (SMART). Detém predominância de β-folha (16,85–37%), seguidas de α-Helix (23,3–30,34%) e alças (39,5–52,81%). O estudo de docking molecular mostrou energia favorável a interação entre Mo-chi1 e GlcNAc com E-valor = -5.9 kcal.mol-1. Embora a Mo-chi1 tenha apresentado propriedades físico-químicas semelhantes a outras quitinases GH18, são necessários estudos mais refinados a fim de identificar seu real potencial.

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PENDEKATAN IN SILICO DALAM MENYINGKAP POTENSI ANTIKANKER MECIADANOL

Jurnal Kimia Riset ◽

10.20473/jkr.v6i2.31071 ◽

2021 ◽

Vol 6 (2) ◽

pp. 163

Author(s):

Arif Fadlan ◽

Tri Warsito ◽

Sarmoko Sarmoko

Keyword(s):

Protein Kinase ◽

In Silico ◽

Autodock Vina ◽

Death Associated Protein Kinase

Meciadanol merupakan flavanol katekin termetilasi pada posisi C3 yang mampu menghambat pembentukan histamin oleh histidin dekarboksilase. Senyawa ini merupakan target menarik dalam pengembangan agen antikanker karena histamin diketahui terlibat dalam perkembangan kanker. Histamin juga dilaporkan dapat berkaitan dengan death associated protein kinase 1 (DAPK1) yang berhubungan dengan apoptosis. Penelitian ini mempelajari potensi aktivitas antikanker meciadanol terhadap DAPK1 secara in silico. Penambatan molekul terhadap protein DAPK1 (kode 5AUX dan 5AV3) dilakukan dengan Autodock Vina yang dilanjutkan dengan evaluasi sifat fisikokimia dan profil ADMET menggunakan SwissADME dan pkCSM. Nilai afinitas ikatan meciadanol terhadap 5AUX dan 5AV3 masing-masing sebesar -7,4 kkal/mol dan -7,0 kkal/mol. Meciadanol selanjutnya tidak melanggar aturan Lipinski, Ghose, Veber, Egan dan Muegge, dan memiliki profil ADMET yang baik berdasarkan deskriptor evaluasi.

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Discovery of Potential Plant-derived Iradoides with COVID-19 Mpro in silico

10.21203/rs.3.rs-512993/v1 ◽

2021 ◽

Author(s):

Mohd Rehan

Keyword(s):

Natural Products ◽

Chinese Medicine ◽

In Silico ◽

Binding Energies ◽

Small Class ◽

Chinese Scientist ◽

Autodock Vina ◽

Discovery Studio ◽

Traditional System ◽

Potential Target

Abstract Iradoides are a small class of plant derived natural products, which used in traditional system of medicine such as Unani, Tibetan, Ayurveda, Siddha, and Chinese medicine. The several diverse types of iradoides have been isolated from many parts of the plant such as root, leaves, flowers, stem, rhizomes, bark, and seed. Here, we used bioactive iradoides to know the potency against COVID-19 Mpro. The COVID-19 Mpro is a potential target of the drug, which identified by Chinese scientist (published manuscript in Nature on June 2020). From several studies, we found that many natural products such as flavonoids, saponins, steroids, terpenoids, and synthesized compounds have been used on this target (COVID-19 Mpro). We screened a series of iradoides against COVID-19 Mpro (PDB ID: 6LU7) by using many docking software as BIOVIA Discovery Studio 2017 R2, Chimera 1.13.1, Auto Dock Tools-1.5.6, AutoDock Vina to known best inhibitor against COVID-19 Mpro. According to obtained results, 6′-O-trans-feruloylnegundoside, p-hydroxybenzoyl-6′-O-trans-caffeoylgardoside, 2′-O-p-hydroxybenzoyl gardoside, 6-deoxyharpagide, reptoside show binding energies -8.1, -8.3, -8.2, -7.0, and -7.1 Kcal/mol, respectively. From this study, we found that all iradoides show more potency on COVID-19 Mpro when compared with Chloroquine and hydroxychloroquine. The Chloroquine and hydroxychloroquine used as standards for comparison. From the results of this study, we found that iradoides may be useful in the treatment of COVID-19 patients.

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In silico analysis of the supposed absence of therapeutic synergism in the association of hydroxychloroquine and azithromycin in COVID-19

Research Society and Development ◽

10.33448/rsd-v9i11.9712 ◽

2020 ◽

Vol 9 (11) ◽

pp. e2249119712

Author(s):

Bruna Fernandes ◽

Luan Gabriel Pinto ◽

Ériky Fernandes Guimarães Silva ◽

Angélica De Fátima Marcussi ◽

Anderson Dillmann Groto ◽

...

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Autodock Vina ◽

Silico Analysis

A associação terapêutica entre hidroxicloroquina (HCQ) e azitromicina (AZI) foi considerada como terapia para COVID-19, no entanto, não está claro se ocorre uma ação sinérgica. Para melhor compreender esta associação terapêutica, este estudo teve como objetivo analisar a interação do HCQ e AZI com receptores humanos in silico.. A análise foi realizada por simulação de docking molecular. As interações químicas do HCQ e AZI com prováveis receptores no organismo humano, ACE2 e CD147, foram analisadas no software AutoDock Vina e os resultados analisados no software PyMol. Os conformadores HCQ-ACE2 e AZI-CD147 foram formados com energia de afinidade significativa de -7,0 Kcal / mol e -7,8 Kcal / mol, respectivamente. Apesar da interação entre HCQ e ACE2 poder prevenir a invasão das células pelo vírus, essa interação pode levar a efeitos colaterais graves. Por sua vez, a interação AZI-CD147 também pode atuar impedindo a entrada do vírus nas células. Além disso, de acordo com o in silicodados, a interação AZI-CD147 ocorreria de forma mais eficaz, o que leva a crer que a ação terapêutica do HCQ no COVID-19 não é tão relevante quanto a ação do AZI e não haveria sinergismo.

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