scholarly journals Corrigendum: Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Perumal Gobinath ◽  
Ponnusamy Packialakshmi ◽  
Kaliappillai Vijayakumar ◽  
Magda H. Abdellattif ◽  
Mohd Shahbaaz ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
In Silico ◽  
Indole Derivatives ◽  
Spike Glycoprotein ◽  
In Silico Screening

scholarly journals Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Perumal Gobinath ◽  
Ponnusamy Packialakshmi ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
Amal Alotaibi ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Normal Cell ◽  
Biological Activities ◽  
Research Work ◽  
Indole Derivatives ◽  
Spike Glycoprotein ◽  
Standard Drug

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a–1j, was synthesized without a catalyst. The products were confirmed by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC50−0.9 μm, MCF−7, LC50−0.55 μm, HeLa, LC50−0.50 μm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC50 > 100 μg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score −2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus.

scholarly journals In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

2020 ◽  
Vol 26 (9) ◽  
pp. 663-669 ◽  
Author(s):  
Tian-zi Wei ◽  
Hao Wang ◽  
Xue-qing Wu ◽  
Yi Lu ◽  
Sheng-hui Guan ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Spike Glycoprotein ◽  
In Silico Screening ◽  
Potential Spike ◽  
Glycoprotein Inhibitors

scholarly journals In silico screening of known small molecules to bind ACE2 specific RBD on Spike Glycoprotein of SARS-CoV-2 for repurposing against COVID-19

2020 ◽  
Author(s):  
Bharath B R ◽  
Hrishikesh Damle ◽  
Shiban Ganju ◽  
LathaDamle
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Md Simulation ◽  
Drug Repurposing ◽  
Cell Receptor ◽  
Docking Studies ◽  
Receptor Interaction ◽  
Spike Glycoprotein ◽  
In Silico Screening ◽  
Novel Drugs

Abstract Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. Although, no effective novel drugs are available, drug repurposing is emerging as an effective strategy. In this study, we present an in silico drug repurposing study implementing successful concepts of computer aided drug design (CADD) technology with an objective to repurpose known drugs to interfere the viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates the virus–cell receptor interaction. SARS-CoV-2-S uses ACE2 to enter cells. Totally, 4015 known and approved small molecules were screened for interaction with SARS-CoV-2 S through docking studies and 15 lead molecules were shortlisted. Further, three molecules streptomycin, ciprofloxacin and Glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability, affordability and subjected for Molecular Dynamics (MD) simulation. The MD simulation results indicate that GA from plant origin may be repurposed against SARS-CoV-2 and further studies are needed for validation.

Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

2019 ◽  
Author(s):  
Veeren Chauhan ◽  
Mohamed M Elsutohy ◽  
C Patrick McClure ◽  
Will Irving ◽  
Neil Roddis ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Point Of Care ◽  
Lateral Flow ◽  
Nucleic Acid Sequence ◽  
In Silico Screening ◽  
Lateral Flow Assays ◽  
Life Threatening ◽  
Software And Hardware ◽  
Nucleic Acid Sequences

<p>Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10<sup>-7</sup> M, ≥1.4×10<sup>-14</sup> g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.</p>

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

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.

In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

2020 ◽  
Vol 20 ◽  
Author(s):  
Dnyaneshwar Baswar ◽  
Abha Sharma ◽  
Awanish Mishra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Cholinergic Neurons ◽  
In Silico Screening ◽  
In Silico Studies ◽  
Bbb Permeability ◽  
Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

In silico Screening and Molecular Interaction Studies of Tetrahydrocannabinol and its Derivatives with Acetylcholine Binding Protein

2018 ◽  
Vol 12 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Priya P. Panigrahi ◽  
Ramit Singla ◽  
Ankush Bansal ◽  
Moacyr Comar Junior ◽  
Vikas Jaitak ◽  
...  
Keyword(s):  
Molecular Interaction ◽  
In Silico ◽  
Binding Protein ◽  
In Silico Screening ◽  
Acetylcholine Binding Protein ◽  
Interaction Studies

scholarly journals Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1H-benzo[g]indole Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4240
Author(s):  
Manar M. Arafeh ◽  
Ebrahim Saeedian Moghadam ◽  
Sirin A. I. Adham ◽  
Raphael Stoll ◽  
Raid J. Abdel-Jalil
Keyword(s):  
Melting Point ◽  
Cytotoxic Activity ◽  
Elemental Analysis ◽  
13C Nmr ◽  
National Cancer Institute ◽  
Polyphosphoric Acid ◽  
Human Cancer ◽  
Indole Derivatives ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

A novel series of 2-(aryldiazenyl)-3-methyl-1H-benzo[g]indole derivatives (3a–f) were prepared through the cyclization of the corresponding arylamidrazones, employing polyphosphoric acid (PPA) as a cyclizing agent. All of the compounds (3a–f) were characterized using 1H NMR, 13C NMR, MS, elemental analysis, and melting point techniques. The synthesized compounds were evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. While all of the screened compounds were found to be cytotoxic at a 10 µM concentration, two of them (2c) and (3c) were subjected to five dose screens and showed a significant cytotoxicity and selectivity.

Pimenta dioica and Pimenta racemosa: GC-based metabolomics for the assessment of seasonal and organs variation in their volatile components, in silico and in vitro cytotoxic activity estimation

2021 ◽  
Author(s):  
Fadia S. Youssef ◽  
Rola Labib ◽  
A. Gad Haidy ◽  
Safaa Eid ◽  
Mohamed Lotfy Ashour ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Cytotoxic Activity ◽  
In Silico ◽  
Volatile Components ◽  
Gas Liquid Chromatography ◽  
Four Seasons ◽  
Pimenta Racemosa ◽  
Pimenta Dioica ◽  
Activity Estimation

Volatile constituents isolated from stems (S) and leaves (L) of Pimenta dioica (PD) and Pimenta racemosa (PR) during the four seasons were analyzed using GLC/FID (Gas liquid chromatography – flame...

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