scholarly journals In silico evaluation of potential inhibitory activity of remdesivir, favipiravir, ribavirin and galidesivir active forms on SARS-CoV-2 RNA polymerase

2021 ◽  
Author(s):  
Ismail Celik ◽  
Meryem Erol ◽  
Zekeriya Duzgun
Keyword(s):  
Rna Polymerase ◽  
Inhibitory Activity ◽  
In Silico

Docking studies of tetra substituted pyrazolone derivatives as potential antiviral agents

2018 ◽  
Vol 5 (2) ◽  
pp. 5-8
Author(s):  
Jyothi Achuthanandhan ◽  
Baskar Lakshmanan
Keyword(s):  
Rna Polymerase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Antiviral Agents ◽  
Docking Studies ◽  
Binding Modes ◽  
Binding Interaction ◽  
Rna Dependent Rna Polymerase ◽  
Adme Prediction ◽  
Pyrazolone Derivatives

In an attempt to find potential antiviral agents, a series of pyrazolones (PA1-PA6& PC1-PC6) were designed and evaluated for their  DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue  PA6showed superior inhibitory activity against RNA dependent RNA polymerase. SAR  study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.

scholarly journals Flavonoids and Nucleotide Analogs Show High Affinity for Viral Proteins of SARS-CoV-2 by in silico Analysis: New Candidates for the Treatment of COVID-19.

2020 ◽  
Author(s):  
Luis Adrián De Jesús-González ◽  
Juan Fidel Osuna-Ramos ◽  
José Manuel Reyes-Ruiz ◽  
Carlos Noe Farfan-Morales ◽  
Selvin Noé Palacios-Rápalo ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Antiviral Drug ◽  
World Health ◽  
Nucleotide Analogs ◽  
High Affinity ◽  
Uridine Nucleotide

Abstract The recent epidemic of COVID-19 caused by SARS-CoV-2 was declared by the World Health Organization as a public health emergency of international concern. The absence of an approved vaccine or a specific antiviral drug has made bioinformatic tools crucial for the identification of potential therapeutic targets and drugs for its control. As in other RNA viruses, the protease 3C-like and the RNA-polymerase are two of the SARS-CoV-2 targets to test drugs that can be analyzed in silico. In the present study, compounds derived from plants, fungi, and nucleoside 5'-triphosphate or uridine nucleotide analogs, with anti-DENV activity in vitro or in vivo, were analyzed by molecular docking as potential anti-SARS-CoV-2 drugs. Anthraquinone, with a DENV NS3 protease inhibitory activity; Balapiravir, Fisetin, Hyperoside, and Sofosbuvir, with a DENV NS5 RNA-polymerase inhibitory activity; and Quercetin, with both anti-NS3-NS5 activities, were tested against 3C-like protease and RNA-polymerase of SARS-CoV-2. All these drugs demonstrated a high affinity for the corresponding SARS-CoV-2 proteins, representing excellent candidates for the treatment of COVID-19. Therefore, in vitro or in vivo studies should be carried out using these compounds on models for SARS-CoV-2 infection.

2,4-Dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic Acid Derivatives: In Vitro Antidiabetic Activity, Molecular Modeling and In silico ADMET Screening

2019 ◽  
Vol 15 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Samridhi Thakral ◽  
Vikramjeet Singh
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Antidiabetic Activity ◽  
Standard Drug ◽  
Benzoic Acid Derivatives ◽  
In Silico Admet ◽  
Inhibitory Potential

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases

2020 ◽  
Vol 20 ◽  
Author(s):  
Trinath Chowdhury ◽  
Gourisankar Roymahapatra ◽  
Santi M. Mandal
Keyword(s):  
Rna Polymerase ◽  
Viral Entry ◽  
In Silico ◽  
Rna Dependent Rna Polymerase ◽  
Replication Complex ◽  
In Silico Study ◽  
Life Threatening ◽  
In Vivo Analysis ◽  
3Cl Protease

Background: COVID-19 is a life threatening novel corona viral infection to our civilization and spreading rapidly. Terrific efforts are generous by the researchers to search for a drug to control SARS-CoV-2. Methods: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Results: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also perform the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). Conclusion: In host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast invitro to in-vivo analysis towards development of therapeutics against SARS-CoV-2.

scholarly journals Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

2021 ◽  
Vol 14 (1) ◽  
pp. 49
Author(s):  
David Méndez-Luna ◽  
Loreley Araceli Morelos-Garnica ◽  
Juan Benjamín García-Vázquez ◽  
Martiniano Bello ◽  
Itzia Irene Padilla-Martínez ◽  
...  
Keyword(s):  
Binding Site ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
New Compounds

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

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