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We evaluated the\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in\u00a0vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID\u201019 infection. We validated the AI\u2010predicted biochemical inhibitory effects of baricitinib on human numb\u2010associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID\u201019 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS\u2010CoV\u20102 viral load, inflammatory markers, and IL\u20106 levels. Collectively, these data support further evaluation of the anti\u2010cytokine and anti\u2010viral activity of baricitinib and support its assessment in randomized trials in hospitalized COVID\u201019 patients.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202012697","type":"journal-article","created":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T18:01:15Z","timestamp":1590861675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":265,"title":["Mechanism of baricitinib supports artificial intelligence\u2010predicted testing in COVID\u201019 patients"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-6947","authenticated-orcid":false,"given":"Justin","family":"Stebbing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3295-6598","authenticated-orcid":false,"given":"Venkatesh","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"de Bono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ottaviani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Casalini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Monteil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker M","family":"Lauschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mirazimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Youhanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee\u2010Joo","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Sarasini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A Ross","family":"Terres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Nickoloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E","family":"Higgs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L","family":"Byers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E","family":"Schlichting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Nirula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabela","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Corbellino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Sacco Baricitinib Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"BFEMMM202012697_CR1","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1172\/JCI89857","volume":"127","author":"E Bekerman","year":"2017","unstructured":"Bekerman E, Neveu G, Shulla A, Brannan J, Pu SY, Wang S, Xiao F, Barouch\u2010Bentov R, Bakken RR, Mateo R et\u00a0al (2017) Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad\u2010spectrum antiviral effects. 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JS has sat on a number of scientific advisory boards, including BenevolentAI, and consults with Lansdowne partners and Vitruvian, and since these findings in patients, consults with Eli Lilly and Company; he sits on the Board of Directors for BB Biotech Healthcare Trust. VML is the founder, CEO, and shareholder of HepaPredict AB. In addition, VML discloses consultancy work for EnginZyme AB. VM, AM, SO, MC, and GC report no conflicts of interest. PJR is an employee of BenevolentAI. VK, SdB, JART, BJN, REH, GR, NLB, DES, AN, and AC are employees and shareholders of Eli Lilly and Company.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMMM202012697"}}