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Network-Based Prediction of Side Effects of Repurposed Antihypertensive Sartans against COVID-19 via Proteome and Drug-Target Interactomes.

作者信息

Kiouri Despoina P, Ntallis Charalampos, Kelaidonis Konstantinos, Peana Massimiliano, Tsiodras Sotirios, Mavromoustakos Thomas, Giuliani Alessandro, Ridgway Harry, Moore Graham J, Matsoukas John M, Chasapis Christos T

机构信息

Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece.

Department of Chemistry, Laboratory of Organic Chemistry, National Kapodistrian University of Athens, 15772 Athens, Greece.

出版信息

Proteomes. 2023 Jun 8;11(2):21. doi: 10.3390/proteomes11020021.


DOI:10.3390/proteomes11020021
PMID:37368467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10305495/
Abstract

The potential of targeting the Renin-Angiotensin-Aldosterone System (RAAS) as a treatment for the coronavirus disease 2019 (COVID-19) is currently under investigation. One way to combat this disease involves the repurposing of angiotensin receptor blockers (ARBs), which are antihypertensive drugs, because they bind to angiotensin-converting enzyme 2 (ACE2), which in turn interacts with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. However, there has been no in silico analysis of the potential toxicity risks associated with the use of these drugs for the treatment of COVID-19. To address this, a network-based bioinformatics methodology was used to investigate the potential side effects of known Food and Drug Administration (FDA)-approved antihypertensive drugs, Sartans. This involved identifying the human proteins targeted by these drugs, their first neighbors, and any drugs that bind to them using publicly available experimentally supported data, and subsequently constructing proteomes and protein-drug interactomes. This methodology was also applied to Pfizer's Paxlovid, an antiviral drug approved by the FDA for emergency use in mild-to-moderate COVID-19 treatment. The study compares the results for both drug categories and examines the potential for off-target effects, undesirable involvement in various biological processes and diseases, possible drug interactions, and the potential reduction in drug efficiency resulting from proteoform identification.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/5501083b19f4/proteomes-11-00021-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/bee6ed8e7e99/proteomes-11-00021-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/bc9456f37da8/proteomes-11-00021-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/0c9bc4078e8b/proteomes-11-00021-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/20a1ce1ea4fc/proteomes-11-00021-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/035a719d5b8a/proteomes-11-00021-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/1a5794b538f0/proteomes-11-00021-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/e167a7c8959b/proteomes-11-00021-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/35288e6931d4/proteomes-11-00021-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/920e13fccaee/proteomes-11-00021-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/2bd9548e3cbb/proteomes-11-00021-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/10c9f8bec77c/proteomes-11-00021-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/0505f0529579/proteomes-11-00021-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/5501083b19f4/proteomes-11-00021-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/bee6ed8e7e99/proteomes-11-00021-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/bc9456f37da8/proteomes-11-00021-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/0c9bc4078e8b/proteomes-11-00021-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/20a1ce1ea4fc/proteomes-11-00021-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/035a719d5b8a/proteomes-11-00021-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/1a5794b538f0/proteomes-11-00021-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/e167a7c8959b/proteomes-11-00021-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/35288e6931d4/proteomes-11-00021-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/920e13fccaee/proteomes-11-00021-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/2bd9548e3cbb/proteomes-11-00021-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/10c9f8bec77c/proteomes-11-00021-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/0505f0529579/proteomes-11-00021-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/10305495/5501083b19f4/proteomes-11-00021-g013.jpg

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Network-Based Prediction of Side Effects of Repurposed Antihypertensive Sartans against COVID-19 via Proteome and Drug-Target Interactomes.

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[9]
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[10]
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本文引用的文献

[1]
Molecular Epidemiology of SARS-CoV-2: The Dominant Role of Arginine in Mutations and Infectivity.

Viruses. 2023-1-22

[2]
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.

Nature. 2023-3

[3]
Paxlovid Information From FDA and Guidance for AES Members.

Epilepsy Curr. 2022-4-4

[4]
Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.

Molecules. 2022-7-29

[5]
Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19.

Int J Mol Sci. 2022-8-4

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Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations.

Vasc Health Risk Manag. 2022

[7]
Paxlovid: Mechanism of Action, Synthesis, and Study.

Biomed Res Int. 2022

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Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.

Rev Esp Quimioter. 2022-8

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Understanding the Driving Forces That Trigger Mutations in SARS-CoV-2: Mutational Energetics and the Role of Arginine Blockers in COVID-19 Therapy.

Viruses. 2022-5-11

[10]
Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications.

Clin Pharmacol Ther. 2022-12

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