scholarly journals SGLT2‐Inhibition reverts urinary peptide changes associated with severe COVID‐19: An in‐silico proof‐of‐principle of proteomics‐based drug repurposing

PROTEOMICS ◽  
2021 ◽  
pp. 2100160
Author(s):  
Agnieszka Latosinska ◽  
Justyna Siwy ◽  
David Z. Cherney ◽  
Bruce A. Perkins ◽  
Harald Mischak ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Sglt2 Inhibition ◽  
Urinary Peptide ◽  
Proof Of Principle

scholarly journals SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: an in-silico proof-of-principle of proteomics-based drug repurposing

2021 ◽  
Author(s):  
Agnieszka Latosinska ◽  
Justyna Siwy ◽  
David Z. Cherney ◽  
Bruce A. Perkins ◽  
Harald Mischak ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Large Degree ◽  
Therapeutic Benefit ◽  
Endothelial Damage ◽  
Randomised Control Trial ◽  
Clinical Test ◽  
Protective Mechanisms ◽  
Sglt2 Inhibition ◽  
Urinary Peptide ◽  
Proof Of Principle

Severe COVID-19 is reflected by significant changes in multiple urine peptides. Based on this observation, a clinical test based on urinary peptides predicting COVID-19 severity, CoV50, was developed and registered as IVD in Germany. We have hypothesized that molecular changes displayed by CoV50, to a large degree likely reflective of endothelial damage, can be significantly reversed by specific drugs. To test this hypothesis, we have collected urinary peptide data from patients without COVID-19 prior and after drug treatment. The drugs chosen were selected based on availability of sufficient number of participants in the dataset (n>20) and potential value of drug therapies in the treatment of COVID-19 based on reports in the literature. In these participants without COVID-19, while spironolactone did not demonstrate a significant impact on CoV50 scoring, empagliflozin treatment resulted in a significant change in CoV50 scoring, indicative of a potential therapeutic benefit. The results serve as a proof-of-principle for a drug repurposing approach based on human urinary peptide signatures and support the initiation of a randomised control trial testing a potential positive effect of empagliflozin in the treatment of severe COVID-19, possibly via endothelial protective mechanisms.

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.

scholarly journals Proteomics advances towards developing SARS-CoV-2 therapeutics using in silico drug repurposing approaches

2021 ◽  
Author(s):  
Amrita Mukherjee ◽  
Ayushi Verma ◽  
Surbhi Bihani ◽  
Ananya Burli ◽  
Krishi Mantri ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease

2021 ◽  
Author(s):  
Nemanja Djokovic ◽  
Dusan Ruzic ◽  
Teodora Djikic ◽  
Sandra Cvijic ◽  
Jelisaveta Ignjatovic ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Main Protease ◽  
Potential Inhibitors

scholarly journals Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel in Silico Method

2020 ◽  
Author(s):  
Milan Sencanski ◽  
Vladimir Perovic ◽  
Snezana Pajovic ◽  
Miroslav Adzic ◽  
Slobodan Paessler ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
In Silico ◽  
Drug Target ◽  
Transmission Rate ◽  
Experimental Testing ◽  
Drug Repurposing ◽  
Global Public Health ◽  
Main Protease ◽  
Additional Approach ◽  
Drugbank Database

<p>The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is <em>in silico</em> drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening (VS) protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the ISM applied for Small Molecules was used for searching the Drugbank database and further followed by molecular docking. After <em>in silico</em> screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.</p>

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