Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform |
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| Authors: | Kaushik Chakravarty Victor G Antontsev Maksim Khotimchenko Nilesh Gupta Aditya Jagarapu Yogesh Bundey Hypatia Hou Neha Maharao Jyotika Varshney |
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| Institution: | VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA; (K.C.); (V.G.A.); (M.K.); (N.G.); (A.J.); (Y.B.); (H.H.); (N.M.) |
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| Abstract: | 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 Ca2+-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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| Keywords: | COVID-19 ACE inhibitors calcium channel blockers artificial intelligence drug repurposing |
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