{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:12:08Z","timestamp":1783350728449,"version":"3.54.6"},"reference-count":77,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/molecules26071912","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T16:01:57Z","timestamp":1617033717000},"page":"1912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0067-7332","authenticated-orcid":false,"given":"Kaushik","family":"Chakravarty","sequence":"first","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-7298","authenticated-orcid":false,"given":"Victor G.","family":"Antontsev","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-9927","authenticated-orcid":false,"given":"Maksim","family":"Khotimchenko","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Jagarapu","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Bundey","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hypatia","family":"Hou","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Maharao","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotika","family":"Varshney","sequence":"additional","affiliation":[{"name":"VeriSIM Life, 1 Sansome Street, Suite 3500, San Francisco, CA 94104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijsu.2020.04.001","article-title":"Evidence based management guideline for the COVID-19 pandemic\u2014Review article","volume":"77","author":"Nicola","year":"2020","journal-title":"Int. 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