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Primary therapy with quinine or artemisinin derivatives is generally effective in controlling<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>parasitemia, but mortality from CM and other forms of severe malaria remains unacceptably high. Herein, we report the design and synthesis of a novel carbon monoxide-releasing molecule (CO-RM; ALF492) that fully protects mice against experimental CM (ECM) and ALI. ALF492 enables controlled CO delivery<jats:italic>in vivo<\/jats:italic>without affecting oxygen transport by hemoglobin, the major limitation in CO inhalation therapy. The protective effect is CO dependent and induces the expression of heme oxygenase-1, which contributes to the observed protection. Importantly, when used in combination with the antimalarial drug artesunate, ALF492 is an effective adjunctive and adjuvant treatment for ECM, conferring protection after the onset of severe disease. This study paves the way for the potential use of CO-RMs, such as ALF492, as adjunctive\/adjuvant treatment in severe forms of malaria infection.<\/jats:p>","DOI":"10.1128\/aac.05571-11","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T05:21:18Z","timestamp":1323753678000},"page":"1281-1290","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["A Novel Carbon Monoxide-Releasing Molecule Fully Protects Mice from Severe Malaria"],"prefix":"10.1128","volume":"56","author":[{"given":"Ana C.","family":"Pena","sequence":"first","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Nuno","family":"Penacho","sequence":"additional","affiliation":[{"name":"Alfama Lda., Porto Salvo, Portugal"}]},{"given":"Liliana","family":"Mancio-Silva","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"},{"name":"Unidade de Mal\u00e1ria, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Rita","family":"Neres","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Jo\u00e3o D.","family":"Seixas","sequence":"additional","affiliation":[{"name":"Alfama Lda., Porto Salvo, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica da Universidade Nova de Lisboa, Oeiras, Portugal"}]},{"given":"Afonso C.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Carlos C.","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Alfama Lda., Porto Salvo, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica da Universidade Nova de Lisboa, Oeiras, Portugal"}]},{"given":"Maria M.","family":"Mota","sequence":"additional","affiliation":[{"name":"Unidade de Mal\u00e1ria, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Gon\u00e7alo J. 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