Screening of phytochemicals from Curcuma longa for their inhibitory activity on SARS-CoV-2: An in-silico study

Introduction: Natural products or phytochemicals have always been useful as effective therapeutics and for providing the lead for rational drug discovery approaches specific to anti-viral therapeutics. Methods: The ongoing pandemic caused by novel coronavirus has created a demand for effective therapeutics. Thus, to achieve the primary objective to search for effective anti-viral therapeutics, in silico screening of phytochemicals present in Curcuma longa extract (ex. Curcumin) has been planned. Results: The present work involves the evaluation of ADME properties and molecular docking studies. Conclusion: The application of rationalized drug discovery approaches to screen the diverse natural resources will speed up the anti-COVID drug discovery efforts and benefit the global community.

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In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

Current Proteomics ◽

10.2174/1570164616666190401204009 ◽

2020 ◽

Vol 17 (1) ◽

pp. 40-50

Author(s):

Farzane Kargar ◽

Amir Savardashtaki ◽

Mojtaba Mortazavi ◽

Masoud Torkzadeh Mahani ◽

Ali Mohammad Amani ◽

...

Keyword(s):

Phylogenetic Tree ◽

In Silico ◽

Alpha Helix ◽

In Silico Analysis ◽

Glycogen Storage ◽

Docking Studies ◽

Random Coil ◽

Special Topic ◽

Industrial Biotechnology ◽

In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

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Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200923143935 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bichismita Sahu ◽

Santosh Kumar Behera ◽

Rudradip Das ◽

Tanay Dalvi ◽

Arnab Chowdhury ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Peptide Nucleic Acid ◽

Large Set ◽

Nonstructural Proteins ◽

In Silico Screening ◽

Replication Process ◽

Enveloped Virus ◽

Treatment Regimens ◽

Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

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High throughput in-silico screening of large ligand databases for rational drug design

Modern Methods for Theoretical Physical Chemistry of Biopolymers ◽

10.1016/b978-044452220-7/50073-3 ◽

2006 ◽

pp. 179-189

Author(s):

H. Merlitz ◽

B. Fischer ◽

W. Wenzel

Keyword(s):

Drug Design ◽

High Throughput ◽

In Silico ◽

Rational Drug Design ◽

In Silico Screening ◽

Rational Drug

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A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments

International Journal of Molecular Sciences ◽

10.3390/ijms20184648 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4648 ◽

Cited By ~ 5

Author(s):

Nathalie Lagarde ◽

Elodie Goldwaser ◽

Tania Pencheva ◽

Dessislava Jereva ◽

Ilza Pajeva ◽

...

Keyword(s):

Drug Discovery ◽

Virtual Screening ◽

Web Service ◽

Molecular Mechanics ◽

In Silico ◽

Chemical Biology ◽

In Silico Screening ◽

Web Based ◽

Screening Experiments ◽

The Web

Chemical biology and drug discovery are complex and costly processes. In silico screening approaches play a key role in the identification and optimization of original bioactive molecules and increase the performance of modern chemical biology and drug discovery endeavors. Here, we describe a free web-based protocol dedicated to small-molecule virtual screening that includes three major steps: ADME-Tox filtering (via the web service FAF-Drugs4), docking-based virtual screening (via the web service MTiOpenScreen), and molecular mechanics optimization (via the web service AMMOS2 [Automatic Molecular Mechanics Optimization for in silico Screening]). The online tools FAF-Drugs4, MTiOpenScreen, and AMMOS2 are implemented in the freely accessible RPBS (Ressource Parisienne en Bioinformatique Structurale) platform. The proposed protocol allows users to screen thousands of small molecules and to download the top 1500 docked molecules that can be further processed online. Users can then decide to purchase a small list of compounds for in vitro validation. To demonstrate the potential of this online-based protocol, we performed virtual screening experiments of 4574 approved drugs against three cancer targets. The results were analyzed in the light of published drugs that have already been repositioned on these targets. We show that our protocol is able to identify active drugs within the top-ranked compounds. The web-based protocol is user-friendly and can successfully guide the identification of new promising molecules for chemical biology and drug discovery purposes.

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