scholarly journals Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes

2020 ◽  
pp. 1-13 ◽  
Author(s):  
Ammar D. Elmezayen ◽  
Anas Al-Obaidi ◽  
Alp Tegin Şahin ◽  
Kemal Yelekçi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
In Silico Screening

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 Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method

2021 ◽  
Author(s):  
Milan Sencanski ◽  
Vladimir Perovic ◽  
Jelena Milicevic ◽  
Tamara Todorovic ◽  
Radivoje Prodanovic ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Target ◽  
Experimental Testing ◽  
Drug Repurposing ◽  
Innate Immune ◽  
Host Immune System ◽  
In Silico Screening ◽  
Safe Approach ◽  
Very High ◽  
Drugbank Database

The need for an effective drug against COVID-19, is, after almost 18 months since the global pandemics outburst, still very high. A very quick and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes vi-ral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and there-fore is an attractive drug target. In this study, we used a combined in silico virtual screening candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

scholarly journals Identification of SARS-CoV-2 Papain-like protease (PLpro) inhibitors using combined computational approach

2021 ◽  
Author(s):  
Milan Sencanski ◽  
Vladimir Perovic ◽  
Jelena Milicevic ◽  
Tamara Todorovic ◽  
Radivoje Prodanovic ◽  
...  
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Drug Target ◽  
Experimental Testing ◽  
Drug Repurposing ◽  
Innate Immune ◽  
Host Immune System ◽  
In Silico Screening ◽  
Safe Approach ◽  
Drugbank Database

In the current pandemic finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

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>

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

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