{"id":95471,"date":"2020-03-24T18:25:20","date_gmt":"2020-03-24T17:25:20","guid":{"rendered":"http:\/\/semmelweis.hu\/hirek\/?p=95471"},"modified":"2020-03-25T14:15:23","modified_gmt":"2020-03-25T13:15:23","slug":"a-klorokin-hatasa-a-covid-19-ellen","status":"publish","type":"post","link":"https:\/\/semmelweis.hu\/hirek\/2020\/03\/24\/a-klorokin-hatasa-a-covid-19-ellen\/","title":{"rendered":"A klorokin hat\u00e1sa a COVID-19 ellen"},"content":{"rendered":"<div class=\"lead\">Leg\u00fajabb publik\u00e1ci\u00f3k al\u00e1t\u00e1masztj\u00e1k azon hipot\u00e9zist, miszerint a klorokin (chloroquine) jav\u00edthatja a SARS-CoV-2-vel fert\u0151z\u00f6tt betegek klinikai kimenetel\u00e9t.<\/div>\n<p>Ismert hat\u00e9kony ter\u00e1pia hi\u00e1ny\u00e1ban \u00e9s a jelenlegi j\u00e1rv\u00e1ny\u00fcgyi helyzet miatt felmer\u00fclt a hydroxychloroquin\/chloroquine vizsg\u00e1lata, mivel kor\u00e1bban m\u00e1r potens inhibitork\u00e9nt \u00edrt\u00e1k le sz\u00e1mos koronav\u00edrus, k\u00f6zt\u00fck a SARS \u2013CoV-1 eset\u00e9ben.<\/p>\n<p>\u00c9vtizedekig a chloroquine-t els\u0151 vonalbeli ter\u00e1pi\u00e1s \u00e9s profilaktikus szerk\u00e9nt haszn\u00e1lt\u00e1k mal\u00e1ri\u00e1ban, az egyik legt\u00f6bbet fel\u00edrt gy\u00f3gyszerk\u00e9nt a vil\u00e1gon. A hydroxychloroquine \u00e9s a chloroquine farmakokinetik\u00e1ja hasonl\u00f3: gyors gastrointestin\u00e1lis abszorpci\u00f3 \u00e9s ren\u00e1lis elimin\u00e1ci\u00f3 jellemz\u0151, b\u00e1r a klinikai indik\u00e1ci\u00f3ik illetve a toxikus d\u00f3zisaik k\u00fcl\u00f6nb\u00f6z\u0151ek. Mal\u00e1ri\u00e1ban a chloroquine magas d\u00f3zisban r\u00f6vid ideig (magas d\u00f3zis eset\u00e9n toxikus) vagy alacsony d\u00f3zisban hosszabb ideig alkalmazhat\u00f3, ezzel szemben a hydroxychloroquine magas d\u00f3zisban is hosszabb ideig toler\u00e1lhat\u00f3. Tov\u00e1bb\u00e1 a chloroquine autoimmun megbeteged\u00e9sekben is alkalmazhat\u00f3.<\/p>\n<p>A SARS-CoV-2 filogenetikai anal\u00edzise sor\u00e1n kimutatt\u00e1k, hogy k\u00fcl\u00f6nb\u00f6zik (\u223c 80%-ban nukleotid identikus), de m\u00e9gis kapcsolatban \u00e1ll a SARS-COV-1 v\u00edrussal.<\/p>\n<p><strong>A chloroquine antivir\u00e1lis tulajdons\u00e1gai<\/strong><\/p>\n<p>In vitro verzatilis bioakt\u00edv \u00e1gensnek bizonyult sz\u00e1mos RNS v\u00edrus (polio, rabies, HIV, HepA, HepC, influenza A,B; influenza A H5N1; Chikungunya, Zika, Ebola, Lassa, Hendra, Nipa, kr\u00edmi-kong\u00f3i v\u00e9rz\u00e9ses l\u00e1z), illetve DNS v\u00edrus (HepB, HSV) ellen.<\/p>\n<p>A chloroquine in vitro antivir\u00e1lis tulajdons\u00e1gai kimutatt\u00e1k n\u00e9h\u00e1ny v\u00edrussal fert\u0151z\u00f6tt beteg kezel\u00e9se sor\u00e1n, de reproduk\u00e1lhat\u00f3 klinikai tanulm\u00e1nnyal nem igazolt\u00e1k.<\/p>\n<p>A coronav\u00edrusok tekintet\u00e9ben potenci\u00e1lis ter\u00e1pi\u00e1s hat\u00e1st mutatott a SARS-CoV-1 eset\u00e9ben, illetve in vitro g\u00e1tolta a HCoV-229E replik\u00e1ci\u00f3j\u00e1t epithelialis t\u00fcd\u0151 sejtteny\u00e9szetben.<\/p>\n<p><strong>A chloroquine potenci\u00e1lis antivir\u00e1lis hat\u00e1sa a SARS-CoV-2 ellen<\/strong><\/p>\n<p>Nemr\u00e9giben megjelent tanulm\u00e1ny alapj\u00e1n a chloroquine \u00e9s a remdesivir in vitro k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt g\u00e1tolta a SARS-CoV-2 v\u00edrust, mely felveti vizsg\u00e1latukat infekt\u00e1lt betegek eset\u00e9ben is.<\/p>\n<p>A CNCBD (China National Center for Biotechnology Development) javasolta haszn\u00e1lat\u00e1t \u00e9s a tapasztalatok alapj\u00e1n a chloroquine ig\u00e9retesnek bizonyul a COVID-19 ellen. Hat\u00e1s\u00e1t Pekingben, Hunan \u00e9s Guangdong tartom\u00e1nyban vizsg\u00e1lt\u00e1k. El\u0151zetes jelent\u00e9sek alapj\u00e1n megk\u00f6zel\u00edt\u0151leg 100 chloroquine kezel\u00e9sben r\u00e9szes\u00fcl\u0151 beteg eset\u00e9n tapasztaltak gyorsabb l\u00e1z cs\u00f6kken\u00e9st, l\u00e1that\u00f3 javul\u00e1st a t\u00fcd\u0151ben CT felv\u00e9telek alapj\u00e1n, illetve r\u00f6videbb fel\u00e9p\u00fcl\u00e9si id\u0151t a kontrollokhoz k\u00e9pest (s\u00falyos mell\u00e9khat\u00e1s n\u00e9lk\u00fcl). Ezek alapj\u00e1n javasolt\u00e1k a chloroquine felv\u00e9tel\u00e9t a SARS-CoV-2 kezel\u00e9s ir\u00e1nyelvei k\u00f6z\u00e9. Ugyanakkor nem elhanyagolhat\u00f3ak a kumulat\u00edv d\u00f3zist\u00f3l f\u00fcgg\u0151 mell\u00e9khat\u00e1sok (macula retinopathia \u00e9s cardiomiopathia). Jelenleg legal\u00e1bb 10 klinikai vizsg\u00e1latban tesztelik a chloroquine anti-COVID-19 ter\u00e1pi\u00e1s hat\u00e1s\u00e1t.<\/p>\n<p><strong>A chloroquine hat\u00e1smechanizmusa<\/strong><\/p>\n<ul>\n<li>a chloroquine g\u00e1tolja a v\u00edrus bejut\u00e1s\u00e1t a sejtbe a sejtfelsz\u00edni receptor\u00e1hoz val\u00f3 k\u00f6t\u0151d\u00e9s megakad\u00e1lyoz\u00e1s\u00e1val: az in vitro (Vero sejteken) potens anti-SARS-Cov-1 hat\u00e1st a sejtfelsz\u00edni receptor (ACE2, angiotenzin-konvert\u00e1l\u00f3 enzim) glikoliz\u00e1ci\u00f3j\u00e1nak g\u00e1tl\u00e1s\u00e1val magyar\u00e1zz\u00e1k.<\/li>\n<li>g\u00e1tolja v\u00edrus replik\u00e1ci\u00f3 korai szakasz\u00e1t a pH-dependens endosz\u00f3ma-medi\u00e1lt v\u00edrus bel\u00e9p\u00e9s megzavar\u00e1s\u00e1val<\/li>\n<li>megakad\u00e1lyozza a v\u00edrus proteinek poszt-transzl\u00e1ci\u00f3s modifik\u00e1ci\u00f3j\u00e1t<\/li>\n<li>befoly\u00e1solja a v\u00edrus proteinek \u00e9r\u00e9si folyamat\u00e1t \u00e9s a v\u00edrus antig\u00e9n dendritikus sejtek \u00e1ltali felismer\u00e9s\u00e9t<\/li>\n<li>hat\u00e1sa az immunrendszerre a sejtszignaliz\u00e1ci\u00f3 \u00e9s a pro-inflammatorikus citokinek szab\u00e1lyoz\u00e1sa \u00fatj\u00e1n t\u00f6rt\u00e9nik<\/li>\n<\/ul>\n<p>A chloroquin vizsg\u00e1lata sor\u00e1n teh\u00e1t kimutathat\u00f3, hogy k\u00e9pes g\u00e1tolni t\u00f6bb koronav\u00edrus in vitro replik\u00e1ci\u00f3j\u00e1t. Leg\u00fajabb publik\u00e1ci\u00f3k al\u00e1t\u00e1masztj\u00e1k azon hipot\u00e9zist, miszerint jav\u00edthatja a SARS-CoV-2-vel fert\u0151z\u00f6tt betegek klinikai kimenetel\u00e9t. Azokat a molekul\u00e1ris mechanizmusokat, melyekkel el\u00e9rheti ezeket az eredm\u00e9nyeket, sz\u00fcks\u00e9ges tov\u00e1bb vizsg\u00e1lni. Nemr\u00e9giben kimutatt\u00e1k, hogy a SARS-CoV-2 ugyanazt a sejtfelsz\u00edni ACE2-receptort (t\u00fcd\u0151ben, sz\u00edvben, ves\u00e9ben, illetve b\u00e9lben expressz\u00e1lt) haszn\u00e1lja, mint a SARS-CoV-1. Felt\u00e9telezhet\u0151, hogy a chloroquin befoly\u00e1solja az ACE2 receptor glikozil\u00e1ci\u00f3j\u00e1t, ez\u00e1ltal megakad\u00e1lyozva a SARS-CoV-2 k\u00f6t\u0151d\u00e9s\u00e9t a c\u00e9lsejtekhez.<\/p>\n<p>F\u00e1bi\u00e1n Alexandra<br \/>\nForr\u00e1s: <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0924857920300881\" target=\"_blank\" rel=\"noopener noreferrer\">New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Leg\u00fajabb publik\u00e1ci\u00f3k al\u00e1t\u00e1masztj\u00e1k azon hipot\u00e9zist, miszerint a klorokin jav\u00edthatja a SARS-CoV-2-vel fert\u0151z\u00f6tt betegek klinikai kimenetel\u00e9t.<\/p>\n","protected":false},"author":155,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[13],"tags":[2408,4257],"class_list":["post-95471","post","type-post","status-publish","format-standard","hentry","category-egyeb","tag-mki-alairas","tag-koronavirus"],"acf":[],"_links":{"self":[{"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/posts\/95471","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/users\/155"}],"replies":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/comments?post=95471"}],"version-history":[{"count":2,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/posts\/95471\/revisions"}],"predecessor-version":[{"id":95510,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/posts\/95471\/revisions\/95510"}],"wp:attachment":[{"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/media?parent=95471"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/categories?post=95471"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/semmelweis.hu\/hirek\/wp-json\/wp\/v2\/tags?post=95471"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}