Virtual High Throughput Screening to find suitable inhibitors for SARSCoV-2 Main Protease

2020 ◽  
Vol 18 ◽  
Author(s):  
Upasana Phukan ◽  
Nakul Neog ◽  
Minakshi Puzari ◽  
Mohan Sharma ◽  
Saurov Mahanta ◽  
...  
Keyword(s):  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Binding Energies ◽  
Health Concern ◽  
Potential Candidate ◽  
Major Health ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors

Background: SARS-CoV-2 virus which originated in Wuhan and quickly spread across various countries has taken the form of a pandemic. It is now a major health concern among everyone and finding a solution to this problem is of utmost importance. Understanding its origin, transmission, and interaction with different compounds is essential to find probable inhibitors. Objective: The objective of our study was to search for potential inhibitors of the main protease of SARS-CoV-2 and to access their drug-like properties. Methodology: In our study, 1909 ligands were filtered through Lipinski filter and ADMET properties along with mutagenic nature were analysed. They were screened for inhibitory activity against the Main Protease of SARS-CoV-2 using BIOVIA Discovery studio. Results: After virtual high throughput screening, two compounds- apigenin and N-(4-bromophenyl)-7-hydroxy-2- iminochromene-3-carboxamide were found to have promising binding energies as well as –CDOCKER energy scores compared to the reported inhibitor. Conclusion: Apigenin seems to be a potential candidate against the main protease of SARS-CoV-2 and must be considered for further experiments.

scholarly journals MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

2020 ◽  
pp. 174-178
Author(s):  
SHAILENDRA SANJAY SURYAWANSHI ◽  
POOJA BHAVAKANA JAYANNACHE ◽  
RAJKUMAR SANJAY PATIL ◽  
PALLED MS ◽  
ALEGAON SG
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Studies ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors ◽  
Binding Energy Calculations ◽  
Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

Convolutional Neural Network of Atomic Surface Structures to Predict Binding Energies for High-Throughput Screening of Catalysts

2019 ◽  
Author(s):  
Seoin Back ◽  
Junwoong Yoon ◽  
Nianhan Tian ◽  
Wen Zhong ◽  
Kevin Tran ◽  
...  
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Convolutional Neural Network ◽  
High Throughput ◽  
High Throughput Screening ◽  
Binding Energies ◽  
Surface Structures ◽  
Voronoi Polyhedra ◽  
Atomic Surface

We present an application of deep-learning convolutional neural network of atomic surface structures using atomic and Voronoi polyhedra-based neighbor information to predict adsorbate binding energies for the application in catalysis.

scholarly journals Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors

2021 ◽  
Author(s):  
Julian Breidenbach ◽  
Carina Lemke ◽  
Thanigaimalai Pillaiyar ◽  
Laura Schäkel ◽  
Ghazl Al Hamwi ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Main Protease

scholarly journals Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening

2020 ◽  
Author(s):  
Yan Li ◽  
Jinyong Zhang ◽  
Ning Wang ◽  
Haibo Li ◽  
Yun Shi ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Binding Capacity ◽  
Effective Means ◽  
Clinical Applications ◽  
Therapeutic Drugs ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Clinical Drug ◽  
Specific Inhibitors

Abstract2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.

scholarly journals Identification and Characterization of a New Series of Ghrelin O-Acyl Transferase Inhibitors

2017 ◽  
Vol 23 (2) ◽  
pp. 154-163 ◽  
Author(s):  
Mariko Yoneyama-Hirozane ◽  
Kohei Deguchi ◽  
Takeshi Hirakawa ◽  
Tsuyoshi Ishii ◽  
Tomoyuki Odani ◽  
...  
Keyword(s):  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acyl Transferase ◽  
Lead Compound ◽  
Time Resolved ◽  
Acyl Ghrelin ◽  
Antiobesity Drugs ◽  
High Throughput Assay

Ghrelin O-acyl transferase (GOAT; MBOAT4) catalyzes O-acylation at serine-3 of des-acyl ghrelin. Acyl ghrelin is secreted by stomach X/A-like cells and plays a role in appetite and metabolism. Therefore, GOAT has been expected to be a novel antiobesity target because it is responsible for acyl ghrelin production. Here, we report homogeneous time-resolved fluorescence (HTRF) and enzyme-linked immunosorbent assay (ELISA) methods utilizing human GOAT-expressing microsomes as a novel high-throughput assay system for the discovery of hit compounds and optimization of lead compounds. Hit compounds exemplified by compound A (2-[(2,4-dichlorobenzyl)sulfanyl]-1,3-benzoxazole-5-carboxylic acid) were identified by high-throughput screening using the HTRF assay and confirmed to have GOAT inhibitory activity using the ELISA. Based on the hit compound information, the novel lead compound (compound B, (4-chloro-6-{[2-methyl-6-(trifluoromethyl)pyridin-3-yl]methoxy}-1-benzothiophen-3-yl)acetic acid) was synthesized and exhibited potent GOAT inhibition with oral bioavailability. Both the hit compound and lead compound showed octanoyl-CoA competitive inhibitory activity. Moreover, these two compounds decreased acyl ghrelin production in the stomach of mice after their oral administration. These novel findings demonstrate that GOAT is a druggable target, and its inhibitors are promising antiobesity drugs.

High Throughput Nanofluidic Architectures for Nanoparticle Separation

2009 ◽  
Author(s):  
Anmiv S. Prabhu ◽  
Talukder Zaki Jubery ◽  
Kevin Freedman ◽  
Rafael Mulero ◽  
Prashanta Dutta ◽  
...  
Keyword(s):  
High Throughput ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Cholesterol ◽  
Health Concern ◽  
Ldl Apheresis ◽  
Major Health ◽  
Chemically Modified ◽  
Nanoparticle Separation ◽  
Cholesterol Levels

High blood cholesterol levels and associated complications are a major health concern the world over and current techniques to deal with this, especially low density lipoprotein (LDL) apheresis, have significant room for improvement. We had previously reported a proof of concept technique that relies on silicon nitride based solid state nanopores to separate high density lipoprotein (HDL) like particles from LDL like particles. A mathematical model to describe the setup is reported. This model revealed that charge density of the pore surface was critical in determining the efficiency of separation. Accordingly we chemically modified our nanopores with (3-aminopropyl)-triethoxysilane (APTES) to achieve more efficient, high throughput particle separation. Such a technique could make it possible to develop safe and affordable LDL apheresis devices in the future.

scholarly journals Repurposing of FDA Approved Drugs for the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

2020 ◽  
Author(s):  
Abhik Kumar Ray ◽  
Parth Sarthi Sen Gupta ◽  
Saroj Kumar Panda ◽  
Satyaranjan Biswal ◽  
Malay Kumar Rana
Keyword(s):  
Virtual Screening ◽  
Binding Energies ◽  
Great Promise ◽  
Main Protease ◽  
Promising Target ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Fda Approved Drugs

<p>COVID-19, responsible for several deaths, demands a cumulative effort of scientists worldwide to curb the pandemic. The main protease, responsible for the cleavage of the polyprotein and formation of replication complex in virus, is considered as a promising target for the development of potential inhibitors to treat the novel coronavirus. The effectiveness of FDA approved drugs targeting the main protease in previous SARS-COV (s) reported earlier indicates the chances of success for the repurposing of FDA drugs against SARS-COV-2. Therefore, in this study, molecular docking and virtual screening of FDA approved drugs, primarily of three categories: antiviral, antimalarial, and peptide, are carried out to investigate their inhibitory potential against the main protease. Virtual screening has identified 53 FDA drugs on the basis of their binding energies (< -7.0 kcal/mol), out of which the top two drugs Velpatasvir (-9.1 kcal/mol) and Glecaprevir (-9.0 kcal/mol) seem to have great promise. These drugs have a stronger affinity to the SARS-CoV-2 main protease than the crystal bound inhibitor α-ketoamide 13B (-6.7 kcal/mol) or Indinavir (-7.5 kcal/mol) that has been proposed in a recent study as one of the best drugs for SARS-CoV-2. The <i>in-silico</i> efficacies of the screened drugs could be instructive for further biochemical and structural investigation for repurposing. The molecular dynamics studies on the shortlisted drugs are underway. </p>

scholarly journals Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

2020 ◽  
Author(s):  
Ravi Patel ◽  
Akash Vanzara ◽  
Nimisha Patel ◽  
Ajit Vasava ◽  
Sachin Patil ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Active Site ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Crystallographic Structure ◽  
Medicinal Uses ◽  
Main Protease ◽  
Cyathus Stercoreus ◽  
Potential Inhibitors

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

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