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Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection

The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. As novel vaccines are being discovered and developed, small molecule drugs still constitute a viable treatment option for SARS-CoV-...

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Autores principales: Rao, Praveen P. N., Pham, Amy Trinh, Shakeri, Arash, El Shatshat, Amna, Zhao, Yusheng, Karuturi, Rahul C., Hefny, Ahmed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827924/
https://www.ncbi.nlm.nih.gov/pubmed/33430081
http://dx.doi.org/10.3390/ph14010044
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author Rao, Praveen P. N.
Pham, Amy Trinh
Shakeri, Arash
El Shatshat, Amna
Zhao, Yusheng
Karuturi, Rahul C.
Hefny, Ahmed A.
author_facet Rao, Praveen P. N.
Pham, Amy Trinh
Shakeri, Arash
El Shatshat, Amna
Zhao, Yusheng
Karuturi, Rahul C.
Hefny, Ahmed A.
author_sort Rao, Praveen P. N.
collection PubMed
description The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. As novel vaccines are being discovered and developed, small molecule drugs still constitute a viable treatment option for SARS-CoV-2 infections due to their advantages such as superior patient compliance for oral therapies, reduced manufacturing costs and ease of large scale distribution due to better stability and storage profiles. Discovering new drugs for SARS-CoV-2 infections is a time consuming and expensive proposition. In this regard, drug repurposing is an appealing approach which can provide rapid access to therapeutics with proven record of safety and efficacy. We investigated the drug repurposing potential of a library of dipeptidyl peptidase 4 (DPP4) inhibitors which are currently marketed for type-2 diabetes as treatment option for SARS-CoV-2 infections. These computational studies led to the identification of three marketed DPP4 inhibitors; gemigliptin, linagliptin and evogliptin as potential inhibitors of SARS-CoV-2 M(pro) viral cysteine protease. In addition, our computational modeling shows that these drugs have the potential to inhibit other viral cysteine proteases from the beta coronavirus family, including the SAR-CoV M(pro) and MERS-CoV CL(pro) suggesting their potential to be repurposed as broad-spectrum antiviral agents.
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spelling pubmed-78279242021-01-25 Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection Rao, Praveen P. N. Pham, Amy Trinh Shakeri, Arash El Shatshat, Amna Zhao, Yusheng Karuturi, Rahul C. Hefny, Ahmed A. Pharmaceuticals (Basel) Article The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. As novel vaccines are being discovered and developed, small molecule drugs still constitute a viable treatment option for SARS-CoV-2 infections due to their advantages such as superior patient compliance for oral therapies, reduced manufacturing costs and ease of large scale distribution due to better stability and storage profiles. Discovering new drugs for SARS-CoV-2 infections is a time consuming and expensive proposition. In this regard, drug repurposing is an appealing approach which can provide rapid access to therapeutics with proven record of safety and efficacy. We investigated the drug repurposing potential of a library of dipeptidyl peptidase 4 (DPP4) inhibitors which are currently marketed for type-2 diabetes as treatment option for SARS-CoV-2 infections. These computational studies led to the identification of three marketed DPP4 inhibitors; gemigliptin, linagliptin and evogliptin as potential inhibitors of SARS-CoV-2 M(pro) viral cysteine protease. In addition, our computational modeling shows that these drugs have the potential to inhibit other viral cysteine proteases from the beta coronavirus family, including the SAR-CoV M(pro) and MERS-CoV CL(pro) suggesting their potential to be repurposed as broad-spectrum antiviral agents. MDPI 2021-01-08 /pmc/articles/PMC7827924/ /pubmed/33430081 http://dx.doi.org/10.3390/ph14010044 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rao, Praveen P. N.
Pham, Amy Trinh
Shakeri, Arash
El Shatshat, Amna
Zhao, Yusheng
Karuturi, Rahul C.
Hefny, Ahmed A.
Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title_full Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title_fullStr Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title_full_unstemmed Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title_short Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection
title_sort drug repurposing: dipeptidyl peptidase iv (dpp4) inhibitors as potential agents to treat sars-cov-2 (2019-ncov) infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827924/
https://www.ncbi.nlm.nih.gov/pubmed/33430081
http://dx.doi.org/10.3390/ph14010044
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