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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...

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Autores principales: Chakravarty, Kaushik, Antontsev, Victor G., Khotimchenko, Maksim, Gupta, Nilesh, Jagarapu, Aditya, Bundey, Yogesh, Hou, Hypatia, Maharao, Neha, Varshney, Jyotika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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