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Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform
The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Am...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037385/ https://www.ncbi.nlm.nih.gov/pubmed/33805419 http://dx.doi.org/10.3390/molecules26071912 |
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author | Chakravarty, Kaushik Antontsev, Victor G. Khotimchenko, Maksim Gupta, Nilesh Jagarapu, Aditya Bundey, Yogesh Hou, Hypatia Maharao, Neha Varshney, Jyotika |
author_facet | Chakravarty, Kaushik Antontsev, Victor G. Khotimchenko, Maksim Gupta, Nilesh Jagarapu, Aditya Bundey, Yogesh Hou, Hypatia Maharao, Neha Varshney, Jyotika |
author_sort | Chakravarty, Kaushik |
collection | PubMed |
description | The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca(2+)-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis. |
format | Online Article Text |
id | pubmed-8037385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80373852021-04-12 Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform Chakravarty, Kaushik Antontsev, Victor G. Khotimchenko, Maksim Gupta, Nilesh Jagarapu, Aditya Bundey, Yogesh Hou, Hypatia Maharao, Neha Varshney, Jyotika Molecules Article The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca(2+)-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis. MDPI 2021-03-29 /pmc/articles/PMC8037385/ /pubmed/33805419 http://dx.doi.org/10.3390/molecules26071912 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Chakravarty, Kaushik Antontsev, Victor G. Khotimchenko, Maksim Gupta, Nilesh Jagarapu, Aditya Bundey, Yogesh Hou, Hypatia Maharao, Neha Varshney, Jyotika Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title | Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title_full | Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title_fullStr | Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title_full_unstemmed | Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title_short | Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
title_sort | accelerated repurposing and drug development of pulmonary hypertension therapies for covid-19 treatment using an ai-integrated biosimulation platform |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037385/ https://www.ncbi.nlm.nih.gov/pubmed/33805419 http://dx.doi.org/10.3390/molecules26071912 |
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