{"id":4691,"date":"2020-11-13T22:42:00","date_gmt":"2020-11-13T21:42:00","guid":{"rendered":"https:\/\/www.fipwarriors.eu\/?p=4691"},"modified":"2023-03-29T09:50:21","modified_gmt":"2023-03-29T07:50:21","slug":"aktualny-stav-moznosti-liecby-fip-a-maciek-pozitivnych-na-sars-cov-2","status":"publish","type":"post","link":"https:\/\/www.fipwarriors.eu\/en\/aktualny-stav-moznosti-liecby-fip-a-maciek-pozitivnych-na-sars-cov-2\/","title":{"rendered":"Current treatment options for FIP and SARS-CoV-2 positive cats"},"content":{"rendered":"<p class=\"has-small-font-size wp-block-paragraph\">P&ocirc;vodn&yacute; &#269;l&aacute;nok: <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7671703\/\" target=\"_blank\" rel=\"noreferrer noopener nofollow\">Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats<\/a> (13.11.2020)<br>Autori: Aaron M. Izes, Jane Yu, Jacqueline M. Norris, and Merran Govendir<br>Preklad: 22.1.2021<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">Abstrakt<\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Ma&#269;ac&iacute; infek&#269;n&yacute; z&aacute;pal pobru&scaron;nice (<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;Infek&#269;n&aacute; peritonit&iacute;da ma&#269;iek (angl. Feline infectious peritonitis, zau&#382;&iacute;van&aacute; skratka FIP) je infek&#269;n&eacute; ochorenie ma&#269;iek sp&ocirc;sobuj&uacute;ce smr&#357;. N&aacute;zov je mierne zav&aacute;dzaj&uacute;ci, preto&#382;e nejde o z&aacute;pal pobru&scaron;nice (&#269;i&#382;e peritonea), ale o z&aacute;pal ciev (vaskulit&iacute;da). Klinick&eacute; pr&iacute;znaky FIP sa v&scaron;ak &#269;asto prejavuj&uacute; vo forme z&aacute;palu pobru&scaron;nice. V&iacute;rus FIP nap&aacute;da v&scaron;ak aj pohrudnicu &ndash; z toho d&ocirc;vodu je niekedy choroba ozna&#269;ovan&aacute; tie&#382; ako Infek&#269;n&aacute; ma&#269;acia polyserozit&iacute;da (Feline infectious polyserositis).&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/fip\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">FIP<\/a>) je v&iacute;rusom indukovan&eacute;, imunitne sprostredkovan&eacute; ochorenie ma&#269;iek sp&ocirc;soben&eacute; virulentn&yacute;mi biotypmi ma&#269;ac&iacute;ch koronav&iacute;rusov (FCoV), zn&aacute;mymi ako v&iacute;rus ma&#269;acej infek&#269;nej peritonit&iacute;dy (FIPV). Historicky sa na lie&#269;bu FIP doteraz pou&#382;&iacute;vali tri hlavn&eacute; farmakologick&eacute; pr&iacute;stupy: (1) imunomodul&aacute;tory na ne&scaron;pecifick&uacute; stimul&aacute;ciu imunitn&eacute;ho syst&eacute;mu pacienta za &uacute;&#269;elom zmiernenia klinick&yacute;ch &uacute;&#269;inkov v&iacute;rusu prostredn&iacute;ctvom silnej imunitnej odpovede, (2) imunosupres&iacute;vne l&aacute;tky na do&#269;asn&eacute; potla&#269;enie klinick&yacute;ch pr&iacute;znakov, a (3) hum&aacute;nne antiv&iacute;rusov&eacute; lieky p&ocirc;vodne ur&#269;en&eacute; na in&eacute; &uacute;&#269;ely, z ktor&yacute;ch bohu&#382;ia&#318; u &#382;iadneho nebola spo&#318;ahlivo preuk&aacute;zan&aacute; ich &uacute;&#269;nnos&#357; pri lie&#269;be FIPV. Z ned&aacute;vnych &scaron;t&uacute;di&iacute; sk&uacute;maj&uacute;cich &scaron;irokospektr&aacute;lny <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;L&aacute;tka v&yacute;razne spoma&#318;uj&uacute;ca alebo zastavuj&uacute;ca reakciu.&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/inhibitor\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">inhib&iacute;tor<\/a> koronav&iacute;rusovej prote&aacute;zy GC376 a adenoz&iacute;nov&yacute; nukleozidov&yacute; anal&oacute;g GS-441524 vyplynulo, &#382;e viedli u mnoh&yacute;ch pacientov k zv&yacute;&scaron;eniu miery pre&#382;itia a k ich klinick&eacute;mu vylie&#269;eniu. Pr&iacute;stup lek&aacute;rov k t&yacute;mto antiv&iacute;rusov&yacute;m terapi&aacute;m je v&scaron;ak v s&uacute;&#269;asnosti problematick&yacute;, preto&#382;e e&scaron;te nez&iacute;skali registr&aacute;ciu pre veterin&aacute;rne pou&#382;itie. V d&ocirc;sledku toho ost&aacute;va lie&#269;ba FIP na&#271;alej ve&#318;kou v&yacute;zvou. &Uacute;&#269;elom tohto zhrnutia je poskytn&uacute;&#357; inform&aacute;cie  o s&uacute;&#269;asnom stave terapeut&iacute;k pre lie&#269;bu FIP. &#270;alej z d&ocirc;vodu zv&yacute;&scaron;en&eacute;ho z&aacute;ujmu o koronav&iacute;rusy, ktor&yacute; je d&ocirc;sledkom s&uacute;&#269;asnej &#318;udskej pand&eacute;mie, prin&aacute;&scaron;a toto zhrnutie aj inform&aacute;cie o domestikovan&yacute;ch ma&#269;k&aacute;ch identifikovan&yacute;ch ako pozit&iacute;vne na SARS-CoV-2.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>K&#318;&uacute;&#269;ov&eacute; slov&aacute;:<\/strong> Ma&#269;ka, infek&#269;n&aacute; peritonit&iacute;da ma&#269;iek, FIP, v&iacute;rus infek&#269;nej peritonit&iacute;dy ma&#269;iek, terapeutik&aacute;, lie&#269;ba, SARS-CoV-2 <\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">1. &Uacute;vod<\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Ma&#269;acia infek&#269;n&aacute; peritonit&iacute;da (FIP) je v&iacute;rusom indukovan&eacute;, imunitne sprostredkovan&eacute; ochorenie s vysokou mierou &uacute;mrtnosti, ktor&eacute; glob&aacute;lne postihuje domestikovan&eacute; ma&#269;ky, ako aj niektor&eacute; div&eacute; ma&#269;kovit&eacute; &scaron;elmy (Addie et al. 2009; Drechsler et al. 2011; Pedersen 2014a). Toto ochorenie je sp&ocirc;soben&eacute; virulentn&yacute;mi biotypmi ma&#269;ac&iacute;ch koronav&iacute;rusov (FCoV), zn&aacute;mymi ako v&iacute;rus ma&#269;acej infek&#269;nej peritonit&iacute;dy (FIPV) (Addie et al. 2009; Drechsler et al. 2011; Pedersen 2014a). FIPV vznik&aacute; neidentifikovan&yacute;mi genetick&yacute;mi zmenami vo FCoV, &#269;o vedie k zv&yacute;&scaron;enej schopnosti replik&aacute;cie v monocytoch a makrof&aacute;goch (Addie et al. 2009; Pedersen 2009). Aj ke&#271; FIP m&ocirc;&#382;e postihn&uacute;&#357; ma&#269;ky v akomko&#318;vek veku, jej v&yacute;skyt je najv&auml;&#269;&scaron;&iacute; u ma&#269;iek mlad&scaron;&iacute;ch ako tri roky, najm&auml; u ma&#269;iek vo veku od &scaron;tyroch do &scaron;estn&aacute;stich mesiacov (Addie et al. 2009; Pedersen 2009). Skuto&#269;n&aacute; <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;&amp;lt;!-- wp:paragraph --&amp;gt;&amp;lt;strong&amp;gt;Prevalencia&amp;lt;\/strong&amp;gt;&nbsp;je &scaron;tatistick&yacute; &#269;&iacute;seln&yacute; (naj&#269;astej&scaron;ie percentu&aacute;lny) term&iacute;n, ktor&yacute; ud&aacute;va v&yacute;skyt ur&#269;it&eacute;ho javu na 100 alebo 1000 &#318;ud&iacute; v ur&#269;itom mieste a &#269;ase. Naj&#269;astej&scaron;ie sa pou&#382;&iacute;va v s&uacute;vislosti s&nbsp;chorobami, m&ocirc;&#382;e to by&#357; v&scaron;ak i ak&yacute;ko&#318;vek in&yacute; jav.&amp;lt;br\/&amp;gt;&amp;lt;!-- \/wp:paragraph --&amp;gt;&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/prevalencia\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">prevalencia<\/a> FIP nie je zn&aacute;ma. Zatia&#318; &#269;o niektor&iacute; autori uv&aacute;dzaj&uacute;, &#382;e pribli&#382;ne u 12%, alebo u jednej z deviatich ma&#269;iek infikovan&yacute;ch FCoV d&ocirc;jde k rozvoju klinick&yacute;ch pr&iacute;znakov FIP (Addie et al. 2009; Pedersen 2014b), tento &uacute;daj bol extrapolovan&yacute; sk&ocirc;r zo &scaron;t&uacute;di&iacute; veterin&aacute;rnych klin&iacute;k, ne&#382; z domestikovanej ma&#269;acej popul&aacute;cie ako celku a nezodpoved&aacute; ter&eacute;nnym odhadom po&#269;tu zaznamenan&yacute;ch pr&iacute;padov v pomere k popul&aacute;cii. Ostatn&eacute; &scaron;t&uacute;die poskytuj&uacute; ni&#382;&scaron;iu prevalenciu FIP. V kontrolnej &scaron;t&uacute;dii trvaj&uacute;cej desa&#357; rokov od roku 1986 do roku 1995 bolo z 397 182 pr&iacute;rastkov prezentovan&yacute;ch severoamerick&yacute;m veterin&aacute;rnym lek&aacute;rskym fakultn&yacute;m nemocniciam pribli&#382;ne 0,55% nov&yacute;ch ma&#269;iek a 0,36% z celkov&eacute;ho po&#269;tu ma&#269;iek boli ma&#269;ky s FIP (Rohrbach et al., 2001). U t&yacute;chto pacientov s FIP bola v&yacute;znamne vy&scaron;&scaron;ia pravdepodobnos&#357;, &#382;e i&scaron;lo o &#269;istokrvn&yacute;ch, mlad&yacute;ch a sexu&aacute;lne intaktn&yacute;ch samcov (Rohrbach et al. 2001; Pesteanu-Somogyi et al. 2006). V &scaron;t&uacute;dii sk&uacute;maj&uacute;cej pr&iacute;rastky ma&#269;iek na North Carolina State University College of Veterinary Medicine po&#269;as &scaron;estn&aacute;s&#357;ro&#269;n&eacute;ho obdobia od roku 1986 do roku 2002 z 11 535 vy&scaron;etren&yacute;ch ma&#269;iek zn&aacute;meho plemena, bola prevalencia podozrenia alebo potvrdenia FIP u popul&aacute;cie zmie&scaron;an&yacute;ch plemien ma&#269;iek 0,35% oproti 1,3% v popul&aacute;cii &#269;istokrvn&yacute;ch ma&#269;iek (Pesteanu-Somogyi et al. 2006). U niektor&yacute;ch z t&yacute;chto &scaron;t&uacute;di&iacute; bola diagn&oacute;za FIP stanoven&aacute; na z&aacute;klade samotn&eacute;ho klinick&eacute;ho vy&scaron;etrenia a bez potvrdzuj&uacute;cich diagnostick&yacute;ch testov (Rohrbach et al. 2001; Pesteanu-Somogyi et al. 2006). V austr&aacute;lskej &scaron;t&uacute;dii boli medzi pr&iacute;padmi FIP v&yacute;znamne nadmerne zast&uacute;pen&eacute; mlad&eacute; ma&#269;ky (Worthing et al. 2012). V porovnan&iacute; s popul&aacute;ciou austr&aacute;lskych ma&#269;iek boli v&yacute;razne nedostato&#269;ne zast&uacute;pen&eacute; dom&aacute;ce kr&iacute;&#382;en&eacute;, perzsk&eacute; a himal&aacute;jske ma&#269;ky, zatia&#318; &#269;o nieko&#318;ko plemien malo nadmern&eacute; zast&uacute;penie, vr&aacute;tane plemien Britsk&aacute; kr&aacute;tkosrst&aacute;, Devon Rex a Habe&scaron;sk&aacute; ma&#269;ka. V&yacute;znamne vy&scaron;&scaron;&iacute; podiel FIP bol pozorovan&yacute; u samcov (Worthing et al. 2012).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">FIP je kategorizovan&aacute; pod&#318;a klinick&eacute;ho prejavu bu&#271; ako vlhk&aacute; (efuz&iacute;vna), alebo such&aacute; (neef&uacute;z&iacute;vna) forma (Addie et al. 2009; Pedersen 2009, 2014a). Vlhk&aacute; forma je charakterizovan&aacute; imunitne sprostredkovanou fibrin&oacute;zno-granulomat&oacute;znou serozit&iacute;dou, &#269;asto s v&yacute;potkami bohat&yacute;mi na bielkoviny v hrudnej alebo bru&scaron;nej dutine (Addie et al. 2009; Pedersen 2009, 2014a). Na rozdiel od toho je such&aacute; forma typick&aacute; pyogranulomat&oacute;znymi l&eacute;ziami nach&aacute;dzaj&uacute;cimi sa vo viacer&yacute;ch telesn&yacute;ch org&aacute;noch a okolo krvn&yacute;ch ciev (Addie et al. 2009; Pedersen 2009, 2014a).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&Uacute;mrtnos&#357; spojen&aacute; s FIP je extr&eacute;mne vysok&aacute;, akon&aacute;hle sa objavia klinick&eacute; pr&iacute;znaky (Pedersen 2014b). Ako poznamenal Pedersen (2014b, s. 1333), &bdquo;n&aacute;stup vidite&#318;n&yacute;ch prejavov choroby je sign&aacute;lom, &#382;e boj ma&#269;ky s v&iacute;rusom je prehran&yacute;.&ldquo; Aj ke&#271; niektor&eacute; ma&#269;ky m&ocirc;&#382;u &#382;i&#357; s FIP nieko&#318;ko t&yacute;&#382;d&#328;ov, mesiacov alebo niekedy aj rokov ( Pedersen 2014b), &#269;asy pre&#382;itia sa v&scaron;eobecne l&iacute;&scaron;ia od dn&iacute; do t&yacute;&#382;d&#328;ov pre ef&uacute;znu FIP a t&yacute;&#382;dne a&#382; mesiace pre neef&uacute;znu (such&uacute;) FIP (Fischer et al. 2011; Tsai et al. 2011; Hugo a Heading 2015). Stanovenie definit&iacute;vnej ante-mortem diagn&oacute;zy FIP je n&aacute;ro&#269;n&eacute;, najm&auml; preto, &#382;e s&uacute;&#269;asn&eacute; diagnostick&eacute; testy nedok&aacute;&#382;u rozl&iacute;&scaron;i&#357; medzi FCoV a FIPV (Fischer et al. 2011; Pedersen 2014b). Preto&#382;e sa potvrden&aacute; diagn&oacute;za spolieha pri cytol&oacute;gii a histopatol&oacute;gii na pozit&iacute;vne imunozfarbenie antig&eacute;nu FCoV, m&ocirc;&#382;u by&#357; u chor&yacute;ch ma&#269;iek pre potvrdenie diagn&oacute;zy potrebn&eacute; invaz&iacute;vne diagnostick&eacute; testy na odber tkanivov&yacute;ch biopsi&iacute;. (Tasker 2018). &#268;itate&#318;a odkazujeme na na ned&aacute;vne zhrnutie podrobnej&scaron;&iacute;ch inform&aacute;ci&iacute; o diagnostike FIP (Drechsler et al. 2011; Pedersen 2014b; Tasker 2018; Kennedy 2020). Pri sk&uacute;man&iacute; mo&#382;nost&iacute; lie&#269;by FIP je ve&#318;a star&scaron;&iacute;ch &scaron;t&uacute;di&iacute; popisuj&uacute;cich potenci&aacute;lnu lie&#269;bu v&auml;&#269;&scaron;inou zalo&#382;en&yacute;ch na pr&iacute;padoch bez potvrdenej diagn&oacute;zy FIP a trpiacich nedostatokom spr&aacute;vne kontrolovan&yacute;ch klinick&yacute;ch testov (Hartmann a Ritz 2008). Rovnako je pou&#382;itie &#271;al&scaron;&iacute;ch uv&aacute;dzan&yacute;ch mo&#382;nost&iacute; lie&#269;by v s&uacute;&#269;asnosti podporovan&eacute; iba &scaron;t&uacute;diami <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;in vitro - lat. &amp;quot;V skle&amp;quot; tj. V sk&uacute;mavke, za umel&yacute;ch, laborat&oacute;rnych podmienok. Napr. pri testovan&iacute; &uacute;&#269;inkov chemick&yacute;ch l&aacute;tok na &#382;iv&yacute; organizmus s&uacute; &uacute;&#269;inky sk&uacute;man&eacute; najprv na kult&uacute;re buniek pestovan&yacute;ch v sk&uacute;mavke. In&yacute;m pr&iacute;kladom je oplodnenie in vitro &amp;quot;die&#357;a zo sk&uacute;mavky&amp;quot;, IVF. Porov. in vivo lat. in v; VITRUM sklo&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/in-vitro\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">in vitro<\/a>, a nie klinick&yacute;mi &scaron;t&uacute;diami <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;in vivo - lat. &amp;quot;V &#382;ivom&amp;quot;, v &#382;ivom organizme, &#318;udskom alebo zvieracom. M&ocirc;&#382;e sa t&yacute;ka&#357; ako pokuse aj skuto&#269;n&eacute;ho priebehu ur&#269;it&eacute;ho deja alebo choroby. Porov. in vitro lat. in v; Vivus &#382;iv&yacute;&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/in-vivo\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">in vivo<\/a> (Choong et al. 2014; Doki et al. 2016; Hu et al. 2017; Takano et al. 2017). Napriek ned&aacute;vnym antiv&iacute;rusov&yacute;m &scaron;t&uacute;di&aacute;m s GC376 a GS-441524, ktor&eacute; predstavuj&uacute; ve&#318;k&yacute; pr&iacute;s&#318;ub pri lie&#269;be FIPV u prirodzene a experiment&aacute;lne infikovan&yacute;ch ma&#269;iek (Murphy a kol. 2018; Pedersen a kol. 2018, 2019), tieto l&aacute;tky zatia&#318; nez&iacute;skali registr&aacute;ciu pre veterin&aacute;rne pou&#382;itie (Wogan 2019a , 2019b). Veterin&aacute;rni lek&aacute;ri preto v s&uacute;&#269;asnosti nemaj&uacute; leg&aacute;lne k dispoz&iacute;cii &#382;iadnu &uacute;&#269;inn&uacute; lie&#269;bu proti FIP (Pedersen 2019a).<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">2. SARS-CoV-2<\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">V s&uacute;&#269;asnosti sme svedkami ve&#318;k&eacute;ho z&aacute;ujem o potenci&aacute;l v&iacute;rusu z&aacute;va&#382;n&eacute;ho ak&uacute;tneho respira&#269;n&eacute;ho syndr&oacute;mu druh&eacute;ho typu (SARS-CoV-2) infikova&#357; zvierat&aacute;, vr&aacute;tane hl&aacute;sen&iacute; o domestikovan&yacute;ch a zoologick&yacute;ch chovoch div&yacute;ch ma&#269;iek s pozit&iacute;vnym v&yacute;sledkom na tento v&iacute;rus (Hosie a kol. 2020; USA). Ministerstvo po&#318;nohospod&aacute;rstva 2020; Wang a kol. 2020). Koronav&iacute;rusy s&uacute; jednovl&aacute;knov&eacute; <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;Ribonukleov&aacute; kyselina. Polymern&iacute; makromolekula, jej&iacute;&#382; z&aacute;kladn&iacute;mi stavebn&iacute;mi jednotkami jsou ribonukleotidy. Je sou&#269;&aacute;st&iacute; v&scaron;ech bun&#283;k a slou&#382;&iacute; k p&#345;enosu informac&iacute; z DNA d&aacute;le do bu&#328;ky. Existuje mnoho druh&#367; RNA s r&#367;zn&yacute;mi funkcemi. Mezi nejzn&aacute;mn&#283;j&scaron;&iacute; pat&#345;&iacute; mRNA (medi&aacute;torov&aacute;), tRNA (transferov&aacute;) a rRNA (ribozom&aacute;ln&iacute;).&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/rna\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">RNA<\/a> v&iacute;rusy (Lundstrom 2020) klasifikovan&eacute; do &scaron;tyroch rodov na z&aacute;klade genotypovej a s&eacute;rologickej charakteriz&aacute;cie (Alphacoronavirus, Betacoronavirus, Gammacoronavirus a Deltacoronavirus; Woo et al. 2012). Zatia&#318; &#269;o FCoV je alfa-koronav&iacute;rus (Felten a Hartmann 2019), SARS-CoV-2, ktor&yacute; sp&ocirc;sobuje COVID-19, je beta-koronav&iacute;rus (Chakraborty a Maity 2020; Lai et al. 2020). Koronav&iacute;rusy maj&uacute; vysok&uacute; frekvenciu rekombin&aacute;cie aj inherentne vysok&eacute; r&yacute;chlosti mut&aacute;ci&iacute;, ktor&eacute; im umo&#382;&#328;uj&uacute; r&yacute;chlo sa adaptova&#357; so zv&yacute;&scaron;en&yacute;m potenci&aacute;lom infikova&#357; nov&yacute;ch hostite&#318;ov (Woo et al. 2006). V&iacute;rusov&aacute; rekombin&aacute;cia je &#269;iasto&#269;ne sprostredkovan&aacute; korekt&iacute;vnou aktivitou nsp14 exoribonukle&aacute;zy, u ktorej sa predt&yacute;m preuk&aacute;zalo, &#382;e brzd&iacute; v&yacute;voj lie&#269;by koronav&iacute;rusov na b&aacute;ze nukleozidov (Agostini et al. 2018).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Domestikovan&eacute; ma&#269;ky, ktor&eacute; mali pozit&iacute;vny test na SARS-CoV-2, boli asociovan&eacute; s majite&#318;mi pozit&iacute;vnymi na SARS-CoV-2 alebo majite&#318;mi s podozren&iacute;m na SARS-CoV-2 (Halfmann et al. 2020; Newman 2020). Mal&yacute; po&#269;et domestikovan&yacute;ch ma&#269;iek pozit&iacute;vnych na SARS-CoV-2 vykazoval respira&#269;n&eacute; pr&iacute;znaky horn&yacute;ch alebo doln&yacute;ch d&yacute;chac&iacute;ch ciest (Sailleau et al. 2020), zatia&#318; &#269;o in&eacute; nemali zjavn&eacute; klinick&eacute; pr&iacute;znaky (Newman 2020; Sailleau et al. 2020; Sit 2020; Sit et al. 2020). V limitovan&yacute;ch experiment&aacute;lnych &scaron;t&uacute;di&aacute;ch, ktor&yacute;ch predmetom je ve&#318;k&eacute; mno&#382;stvo v&iacute;rusov&yacute;ch o&#269;kovac&iacute;ch l&aacute;tkok, sa uv&aacute;dza, &#382;e ma&#269;ky m&ocirc;&#382;u pren&aacute;&scaron;a&#357; SARS-CoV-2 na in&eacute; ma&#269;ky umiestnen&eacute; v rovnakom zariaden&iacute; vzdu&scaron;nou cestou (Shi et al. 2020). &#270;al&scaron;ia &scaron;t&uacute;dia uv&aacute;dza, &#382;e o&#269;kovanie a vystavenie &uacute;&#269;inkom SARS-CoV-2 vedie u ma&#269;iek k vylu&#269;ovaniu nosom, a &#382;e ma&#269;ky bez klinick&yacute;ch pr&iacute;znakov s&uacute; schopn&eacute; priameho prenosu v&iacute;rusu na in&eacute; ma&#269;ky (Halfmann et al. 2020). V s&uacute;&#269;asnosti neexistuj&uacute; d&ocirc;kazy o tom, &#382;e by ma&#269;ky mohli pren&aacute;&scaron;a&#357; SARS-CoV-2 na &#269;loveka (Hosie et al. 2020).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ke&#271;&#382;e niektor&eacute; ni&#382;&scaron;ie op&iacute;san&eacute; antivirotik&aacute; preuk&aacute;zali ist&uacute; &uacute;&#269;innos&#357; proti FCoV, je l&aacute;kav&eacute; extrapolova&#357;, &#382;e m&ocirc;&#382;u zn&iacute;&#382;i&#357; aj vylu&#269;ovanie SARS-CoV-2 v zriedkav&yacute;ch pr&iacute;padoch ma&#269;acej infekcie. Pod&#318;a najlep&scaron;&iacute;ch znalost&iacute; autorov v&scaron;ak nie s&uacute; publikovan&eacute; &#382;iadne &scaron;t&uacute;die in vivo na overenie ich antiv&iacute;rusovej aktivity u SARS-COV-2 u ma&#269;ky.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">3. FIP terapeutik&aacute;<\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">V praxi sa na lie&#269;bu FIP pou&#382;&iacute;vaj&uacute; tri hlavn&eacute; pr&iacute;stupy, &#269;i u&#382; jednotlivo alebo v kombin&aacute;cii (Pedersen 2014b). Prv&yacute; pr&iacute;stup sa sna&#382;&iacute; ne&scaron;pecificky modulova&#357; imunitn&yacute; syst&eacute;m pacienta s cie&#318;om zn&iacute;&#382;i&#357; klinick&eacute; &uacute;&#269;inky v&iacute;rusu prostredn&iacute;ctvom silnej imunitnej odpovede (Pedersen 2014b). Druh&yacute; pr&iacute;stup sa spolieha na pou&#382;itie imunosupres&iacute;vnych liekov na tlmenie z&aacute;palovej odpovede, ktor&aacute; je jadrom patol&oacute;gie tohto ochorenia (Hartmann a Ritz 2008; Addie et al. 2009; Pedersen 2014b), zatia&#318; &#269;o tret&iacute; pr&iacute;stup sa zameriava na pou&#382;itie antiv&iacute;rusov&yacute;ch l&aacute;tok inhibuj&uacute;cich replik&aacute;ciu v&iacute;rusov (Murphy et al. 2018; Pedersen et al. 2018, 2019). Aj ke&#271; je mo&#382;n&eacute; ka&#382;d&yacute; z t&yacute;chto hlavn&yacute;ch pr&iacute;stupov pou&#382;i&#357; s&uacute;&#269;asne, ka&#382;d&eacute;mu z nich sa budeme venova&#357; postupne.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">3.1. Ne&scaron;pecifick&eacute; imunostimulanty<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Ne&scaron;pecifick&eacute; imunostimulanty sa pou&#382;&iacute;vaj&uacute; ako lie&#269;ba FIP u&#382; mnoho rokov, &#269;asto kv&ocirc;li nepodlo&#382;en&yacute;m spr&aacute;vam, ktor&eacute; tvrdia, &#382;e tieto re&#382;imy lie&#269;by m&ocirc;&#382;u bu&#271; pred&#314;&#382;i&#357; dobu pre&#382;itia, alebo sl&uacute;&#382;i&#357; ako priamy liek na FIP (Pedersen 2014b). Hlavn&yacute;m cie&#318;om tohto pr&iacute;stupu je stimulova&#357; pacienta, aby vytvoril imunitn&uacute; odpove&#271; nato&#318;ko siln&uacute;, aby dostato&#269;ne zn&iacute;&#382;ila v&iacute;rusov&uacute; n&aacute;lo&#382; na potla&#269;enie klinick&yacute;ch prejavov infekcie. Je v&scaron;ak trochu paradoxn&eacute;, &#382;e pou&#382;itie imunostimulantov sa &#269;asto sp&aacute;ja s imunosupres&iacute;vami, preto&#382;e niektor&eacute; z t&yacute;chto liekov sa m&ocirc;&#382;u vz&aacute;jomne podporova&#357; (Pedersen 2014b). Pr&iacute;klady ne&scaron;pecifick&yacute;ch imunostimulantov pod&aacute;van&yacute;ch ako lie&#269;ba FIP zah&#341;&#328;aj&uacute; stafylokokov&yacute; A prote&iacute;n (Pedersen 2014b), Propionibacterium acnes (imunomodula&#269;n&aacute; zl&uacute;&#269;enina odvoden&aacute; od grampozit&iacute;vnych bakt&eacute;ri&iacute;) (Weiss et al. 1990), imunomodul&aacute;tory T-<a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;&amp;lt;strong&amp;gt;Lymfocyt&amp;lt;\/strong&amp;gt; &ndash; druh b&iacute;l&eacute; krvinky, kter&yacute; se v&yacute;znamn&#283; pod&iacute;l&iacute; na specifick&eacute; imunit&#283; organismu. L. se vyskytuj&iacute; v krvi a v lymfatick&eacute; tk&aacute;ni a d&#283;l&iacute; se na dv&#283; z&aacute;kladn&iacute; skupiny T a B lymfocyty n&#283;kdy se u&#382;&iacute;v&aacute; n&aacute;zvu T a B bu&#328;ky. K funkc&iacute;m T lymfocyt&#367; pat&#345;&iacute; regulace ostatn&iacute;ch bun&#283;k z&uacute;&#269;astn&#283;n&yacute;ch na imunitn&iacute; odpov&#283;di a likvidace choroboplodn&yacute;ch z&aacute;rodk&#367;, pop&#345;. i vlastn&iacute;ch bun&#283;k jimi naka&#382;en&yacute;ch a n&aacute;dor&#367;. B lymfocyty se po setk&aacute;n&iacute; s antigenem a za p&#345;isp&#283;n&iacute; skupiny T lymfocyt&#367; p&#345;em&#283;&#328;uj&iacute; na plasmatick&eacute; bu&#328;ky, kter&eacute; tvo&#345;&iacute; protil&aacute;tky imunoglobuliny. L. p&#345;e&#382;&iacute;vaj&iacute; v organismu dlouhou dobu a tvo&#345;&iacute; tzv. pam&#283;&#357;ov&eacute; bu&#328;ky, kter&eacute; si &amp;quot;pamatuj&iacute;&amp;quot; setk&aacute;n&iacute; s cizorodou l&aacute;tkou antigenem a jsou proti n&iacute; schopny op&#283;t reagovat na tomto principu funguje o&#269;kov&aacute;n&iacute;. P&#345;i v&#283;t&scaron;in&#283; sv&yacute;ch funkc&iacute; spolupracuj&iacute; s makrof&aacute;gy srov. APC, p&#345;i&#269;em&#382; vz&aacute;jemnou komunikaci zprost&#345;edkov&aacute;vaj&iacute; mj. HLA antigeny.&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/lymfocytov\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">lymfocytov<\/a> (ako je omega [&omega;] interfer&oacute;n) (Pedersen 2014b) a rastlinn&eacute; extrakty, ako je polyprenyl imunostimulant (PI) (Legendre a Bartges 2009; Legendre et al. 2017). V&scaron;etky tieto l&aacute;tky boli ne&uacute;spe&scaron;n&eacute; alebo mali pri lie&#269;be FIP iba obmedzen&yacute; efekt. Napr&iacute;klad, pokia&#318; ide o biologick&yacute; rastlinn&yacute; extrakt PI, pou&#382;itie tohto prostriedku p&ocirc;vodne navrhli Legendre a Bartges (2009) po tom, &#269;o sa po dlhodobej lie&#269;be PI &uacute;dajne vylie&#269;ili tri ma&#269;ky zo suchej formy FIP. Tieto v&yacute;skumy v&scaron;ak prip&uacute;&scaron;&#357;aj&uacute;, &#382;e lie&#269;ba nemala &#382;iadny efekt u ma&#269;iek so z&aacute;va&#382;nej&scaron;ou FIP (Legendre a Bartges 2009). Neskor&scaron;ia ter&eacute;nna &scaron;t&uacute;dia PI u 60 ma&#269;iek uk&aacute;zala pred&#314;&#382;en&eacute; &#269;asy pre&#382;itia, pri&#269;om &scaron;tyri z t&yacute;chto ma&#269;iek pre&#382;ili viac ako 300 dn&iacute; so zlep&scaron;enou kvalitou &#382;ivota (Legendre et al. 2017). &Scaron;t&uacute;dia tie&#382; uk&aacute;zala, &#382;e &#269;asy pre&#382;itia s PI boli v&yacute;znamne dlh&scaron;ie u ma&#269;iek, ktor&eacute; neboli s&uacute;&#269;asne lie&#269;en&eacute; kortikosteroidmi (Legendre et al. 2017).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">3.2. Imunosupres&iacute;vne l&aacute;tky<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Pou&#382;itie imunosupres&iacute;vnych l&aacute;tok na tlmenie z&aacute;palovej reakcie u FIPV predstavuje nie&#269;o ako terapeutick&yacute; z&aacute;stupn&yacute; symbol. To znamen&aacute;, &#382;e nedostatok pr&iacute;stupu k bezpe&#269;n&yacute;m a efekt&iacute;vnym alternat&iacute;vam nech&aacute;va veterin&aacute;rnym lek&aacute;rom len ve&#318;mi m&aacute;lo in&yacute;ch mo&#382;nost&iacute;, ako sa spolieha&#357; na imunosupres&iacute;vnu terapiu na potla&#269;enie klinick&yacute;ch pr&iacute;znakov FIP (Hartmann a Ritz 2008; Addie et al. 2009; Pedersen 2014a). Medzi pr&iacute;klady imunosupres&iacute;vnych l&aacute;tok pri lie&#269;be FIP patria glukokortikoidy (napr. Prednizol&oacute;n, dexametaz&oacute;n) (Disque a kol. 1968; Addie a kol. 2009), inhib&iacute;tory <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;Cytokin (podobn&yacute; term&iacute;n interleukin) je ozna&#269;en&iacute; pro skupinu men&scaron;&iacute;ch sign&aacute;ln&iacute;ch protein&#367;, &uacute;&#269;astn&iacute;c&iacute;ch se v&yacute;znamn&#283; v imunitn&iacute; odpov&#283;di. Cytokiny jsou produkov&aacute;ny bu&#328;kami imunitn&iacute;ho syst&eacute;mu (makrof&aacute;gy, T-lymfocyty, atp.) a jsou schopn&eacute; navodit nap&#345;&iacute;klad rychl&eacute; d&#283;len&iacute; a diferenciaci ur&#269;it&yacute;ch typ&#367; bun&#283;k, kter&eacute; se &uacute;&#269;astn&iacute; boje proti patogen&#367;m, p&#345;&iacute;padn&#283; dal&scaron;&iacute; rysy imunitn&iacute; obrany.V ur&#269;it&eacute;m slova smyslu cytokiny nemus&iacute; b&yacute;t produkov&aacute;ny pouze b&iacute;l&yacute;mi krvinkami a v&yacute;znam slova se roz&scaron;i&#345;uje na v&scaron;echny mal&eacute; sign&aacute;ln&iacute; proteiny; term&iacute;n interleukin se v tom p&#345;&iacute;pad&#283; pou&#382;&iacute;v&aacute; pro sign&aacute;ln&iacute; molekuly vylu&#269;ovan&eacute; b&iacute;l&yacute;mi krvinkami.&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/cytokin\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">cytok&iacute;nov<\/a> (napr. Pentoxifyl&iacute;n a propentofyl&iacute;n) (Fischer a kol. 2011) a alkyla&#269;n&eacute; l&aacute;tky (napr. Cyklofosfamid) a chlorambucil) (Bilkei 1988; Addie et al. 2009). Aj ke&#271; pod&aacute;vanie glukokortikoidov redukuje klinick&eacute; pr&iacute;znaky u ma&#269;iek s FIP, neexistuj&uacute; d&ocirc;kazy o tom, &#382;e maj&uacute; u infikovan&yacute;ch ma&#269;iek nejak&yacute; lie&#269;ebn&yacute; efekt (Addie et al. 2009). Tvrdenia, &#382;e l&aacute;tky ako glukokortikoidy s&uacute; &uacute;&#269;inn&eacute; proti FIP, boli vyvr&aacute;ten&eacute; placebom kontrolovan&yacute;mi, dvojito zaslepen&yacute;mi &scaron;t&uacute;diami Ritz a kol. (2007) a Fischer a kol. (2011). V t&yacute;chto &scaron;t&uacute;di&aacute;ch sk&uacute;maj&uacute;cich &uacute;&#269;inky ma&#269;acieho interfer&oacute;nu &omega; (Ritz a kol. 2007) a propentofyl&iacute;nu (Fischer a kol. 2011) na &#269;as pre&#382;itia a kvalitu &#382;ivota ma&#269;iek postihnut&yacute;ch FIP, v&scaron;etky ma&#269;ky (vr&aacute;tane t&yacute;ch, ktor&eacute; boli v skupine s placebom) dost&aacute;vali dexametaz&oacute;n a \/ alebo prednizol&oacute;n. Pr&iacute;slu&scaron;n&iacute; autori uviedli, &#382;e nebol v&yacute;znamn&yacute; rozdiel v dob&aacute;ch pre&#382;itia medzi ma&#269;kami s FIP, ktor&eacute; dost&aacute;vali bu&#271; ma&#269;ac&iacute; interfer&oacute;n &omega; (Ritz et al. 2007), alebo propentofyl&iacute;n (Fischer et al. 2011) (stredn&aacute; doba pre&#382;itia ma&#269;iek interfer&oacute;n &omega; a osem dn&iacute; pre propentofyl&iacute;n) a t&yacute;mi v kontrolnej skupine, ktor&yacute;m sa pod&aacute;vali iba glukokortikoidy (stredn&aacute; doba pre&#382;itia osem dn&iacute; v obidvoch &scaron;t&uacute;di&aacute;ch). Vzh&#318;adom na spolo&#269;n&eacute; pod&aacute;vanie dexametaz&oacute;nu a \/ alebo prednizol&oacute;nu v obidvoch t&yacute;chto &scaron;t&uacute;di&aacute;ch je &#357;a&#382;k&eacute; ur&#269;i&#357; &uacute;&#269;inky ma&#269;acieho interfer&oacute;nu &omega; alebo propentofyl&iacute;nu ako jedin&eacute;ho terapeutick&eacute;ho &#269;inidla. Uk&aacute;zalo sa, &#382;e ma&#269;ac&iacute; interfer&oacute;n &omega; inhibuje replik&aacute;ciu FCoV in vitro (Mochizuki et al. 1994). Nekontrolovan&aacute; &scaron;t&uacute;dia s ma&#269;ac&iacute;m interfer&oacute;nom &omega; a glukokortikoidmi priniesla s&#318;ubn&yacute; v&yacute;sledok u 67% ma&#269;iek, ktor&eacute; dosiahli &uacute;pln&uacute; alebo &#269;iasto&#269;n&uacute; remisiu, ale FIP v t&yacute;chto pr&iacute;padoch nebola potvrden&aacute; (Ishida et al. 2004). Ke&#271; sa rekombinantn&yacute; &#318;udsk&yacute; leukocytov&yacute; interfer&oacute;n alfa alebo ma&#269;ac&iacute; fibroblastick&yacute; beta interfer&oacute;n pou&#382;ili samotn&eacute;, ani jeden z nich nezn&iacute;&#382;il &uacute;mrtnos&#357; u lie&#269;en&yacute;ch ma&#269;iek v porovnan&iacute; s kontroln&yacute;mi (Weiss a Toivio-Kinnucan 1988; Bolcskei a Bilkei 1995; Ritz et al. 2007). Ke&#271; sa v&scaron;ak pou&#382;ila vysok&aacute; d&aacute;vka alfa interfer&oacute;nu v kombin&aacute;cii s Propionibacterium acnes, priemern&aacute; doba pre&#382;itia sa pred&#314;&#382;ila, ale iba o tri t&yacute;&#382;dne (Weiss et al. 1990). V&scaron;eobecne sa s&iacute;ce interfer&oacute;ny &#269;asto pou&#382;&iacute;vaj&uacute; u ma&#269;iek s FIP, ale ich &uacute;&#269;innos&#357; je ot&aacute;zna. Rovnako sa u ma&#269;iek s FIP sk&uacute;malo aj pou&#382;itie cyklofosfamidu v kombin&aacute;cii s prednizol&oacute;nom a ampicil&iacute;nom (Bilkei 1988). Sedemdesiat&scaron;es&#357; zo 151 ma&#269;iek bolo po lie&#269;be pova&#382;ovan&yacute;ch za &bdquo;zdrav&eacute;&ldquo;. Av&scaron;ak ma&#269;ky zahrnut&eacute; do tejto &scaron;t&uacute;die nemali spo&#318;ahlivo potvrden&uacute; diagn&oacute;zu FIP. &#270;al&scaron;ia &scaron;t&uacute;dia sk&uacute;maj&uacute;ca pou&#382;itie cyklofosfamidu okrem prednizol&oacute;nu a ampicil&iacute;nu v pr&iacute;padoch podozrenia na FIP uv&aacute;dza, &#382;e za tri roky uhynulo 29&ndash;80% ma&#269;iek (Bolcskei a Bilkei 1995). U t&yacute;chto ma&#269;iek ale op&auml;&#357; nebola potvrden&aacute; FIP. Ozagrel hydrochlorid (inhib&iacute;tor synt&eacute;zy trombox&aacute;nu) sa tie&#382; pou&#382;il ako imunosupres&iacute;vne &#269;inidlo proti FIP (Watari et al. 1998). Aj ke&#271; sa preuk&aacute;zali priazniv&eacute; &uacute;&#269;inky u dvoch ma&#269;iek, FIP sa nepotvrdila ani u jednej z nich (Watari et al. 1998).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">3.3 . &Scaron;pecifick&eacute; FIP terapeutik&aacute;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Tret&iacute; pr&iacute;stup k lie&#269;be FIP zah&#341;&#328;a pod&aacute;vanie antiv&iacute;rusov&yacute;ch l&aacute;tok zameran&yacute;ch bu&#271; na bunkov&eacute; mechanizmy, ktor&eacute; si v&iacute;rusy vyberaj&uacute; na replik&aacute;ciu, alebo alternat&iacute;vne na &scaron;pecifick&yacute; aspekt aktivity v&iacute;rusu s&uacute;visiaci s infekciou a\/alebo replik&aacute;ciou (Hartmann a Ritz 2008; Addie a kol. 2009; Pedersen 2014a). Boli identifikovan&eacute; antiv&iacute;rusov&eacute; lieky, ktor&eacute; inhibuj&uacute; FCoV, ale mnoh&eacute; z nich neboli u infikovan&yacute;ch pacientov &uacute;spe&scaron;n&eacute; (Weiss et al. 1993; Hartmann a Ritz 2008; Addie et al. 2009; McDonagh et al. 2014; Pedersen 2014b). Pri&scaron;iel v&scaron;ak nov&yacute; terapeutick&yacute; prielom vyu&#382;&iacute;vaj&uacute;ci nukleozidov&yacute; anal&oacute;g GS-441524 s priamym &uacute;&#269;inkom na v&iacute;rus FIP (Murphy a kol. 2018; Pedersen 2019a, 2019b; Dickinson a kol. 2020). GS-441524, akt&iacute;vny metabolit remdesiviru, je termin&aacute;torom re&#357;azca RNA v&iacute;rusovej RNA z&aacute;vislej RNA polymer&aacute;zy (Murphy a kol. 2018; Pedersen a kol. 2019) Uk&aacute;zalo sa, &#382;e silne inhibuje FIPV v tkanivovej kult&uacute;re, v pr&iacute;padoch experiment&aacute;lne infikovan&yacute;ch ma&#269;iek, ako aj u prirodzene z&iacute;skanej FIP (Murphy et al. 2018; Pedersen et al. 2019). Pou&#382;it&iacute;m pr&iacute;stupu in vitro Murphy a kol. (2018) stanovili, &#382;e GS-441524 nevykazuje toxicitu v ma&#269;ac&iacute;ch obli&#269;kov&yacute;ch bunk&aacute;ch Crandell Rees (CRFK) v koncentr&aacute;ci&aacute;ch 100 &micro;M, zatia&#318; &#269;o st&aacute;le bol schopn&yacute; inhibova&#357; replik&aacute;ciu FIPV v kultivovan&yacute;ch bunk&aacute;ch CRFK aj v prirodzene infikovan&yacute;ch ma&#269;ac&iacute;ch peritone&aacute;lnych makrof&aacute;goch v koncentr&aacute;ci&aacute;ch 1,0 &micro;M. V sprievodnej &scaron;t&uacute;dii in vivo na ma&#269;k&aacute;ch experiment&aacute;lne infikovan&yacute;ch FIPV (kme&#328; s&eacute;rotypu I FIPV m3c-2) sa GS-441524 pod&aacute;val jedenkr&aacute;t denne (5,0 mg\/kg BW alebo 2,0 mg\/kg BW ako subkut&aacute;nna injekcia [SC]) po dobu dvoch t&yacute;&#382;d&#328;ov (Murphy et al. 2018). Tento re&#382;im vy&#382;aduj&uacute;ci najmenej dvojt&yacute;&#382;d&#328;ov&uacute; lie&#269;bu viedol k rap&iacute;dnemu zvratu klinick&yacute;ch pr&iacute;znakov a n&aacute;vratu k norm&aacute;lu u v&scaron;etk&yacute;ch pacientov. Nebola zaznamenan&aacute; &#382;iadna toxicita. Na z&aacute;klade tejto pr&aacute;ce Pedersen a kol. (2019) sk&uacute;mali in vivo terapeutick&eacute; &uacute;&#269;inky GS-441524 na prirodzene sa vyskytuj&uacute;cu FIP, vr&aacute;tane vlhkej aj suchej formy ochorenia. Do tejto &scaron;t&uacute;dii bolo prijat&yacute;ch 31 ma&#269;iek (26 s ef&uacute;znou FIP a 5 s neef&uacute;znou FIP) a bola im pod&aacute;van&aacute; d&aacute;vka 2,0 mg\/kg BW SC jedenkr&aacute;t denne po dobu najmenej 12 t&yacute;&#382;d&#328;ov. D&aacute;vka sa zv&yacute;&scaron;ila na 4,0 mg\/kg BW SC jedenkr&aacute;t denne, ke&#271; to indikovali zhor&scaron;uj&uacute;ce sa klinick&eacute; pr&iacute;znaky. &Scaron;tyri ma&#269;ky boli eutanizovan&eacute; alebo uhynuli po&#269;as prv&yacute;ch piatich dn&iacute; experimentu v d&ocirc;sledku z&aacute;va&#382;nosti ich infekcie. Piata ma&#269;ka bola eutanizovan&aacute; po 26 d&#328;och kv&ocirc;li ch&yacute;baj&uacute;cej reakcii na lie&#269;bu. Zvy&scaron;n&yacute;ch 26 ma&#269;iek &uacute;spe&scaron;ne dokon&#269;ilo dvan&aacute;s&#357;t&yacute;&#382;d&#328;ov&yacute; (alebo dlh&scaron;&iacute;) cyklus. Osemn&aacute;s&#357; ma&#269;iek zostalo zdrav&yacute;ch po jednom cykle lie&#269;by, zatia&#318; &#269;o zvy&scaron;n&yacute;ch osem malo relapsy v priebehu 3 a&#382; 84 dn&iacute;. Tri z &ocirc;smich relapsuj&uacute;cich ma&#269;iek boli lie&#269;en&eacute; op&auml;&#357; rovnakou d&aacute;vkou, zatia&#318; &#269;o piatim ma&#269;k&aacute;m bola d&aacute;vka zv&yacute;&scaron;en&aacute; z 2,0 na 4,0 mg \/ kg telesnej hmotnosti. P&auml;&#357; ma&#269;iek lie&#269;en&yacute;ch vy&scaron;&scaron;ou d&aacute;vkou sa uzdravilo. Zo zvy&scaron;n&yacute;ch troch ma&#269;iek lie&#269;en&yacute;ch p&ocirc;vodnou ni&#382;&scaron;ou d&aacute;vkou dve relapsovali druh&yacute;kr&aacute;t a vy&#382;adovali tretiu lie&#269;bu s vy&scaron;&scaron;ou d&aacute;vkou. Tieto dve ma&#269;ky sa uzdravili. Tretia ma&#269;ka relapsovala po druhom kole ni&#382;&scaron;ej d&aacute;vky a bola utraten&aacute; kv&ocirc;li z&aacute;va&#382;nosti svojho neurologick&eacute;ho ochorenia. &Scaron;t&uacute;dia priniesla 25 dlhodobo pre&#382;iv&scaron;&iacute;ch ma&#269;iek. Najbe&#382;nej&scaron;&iacute;m ved&#318;aj&scaron;&iacute;m &uacute;&#269;inkom boli reakcie v mieste vpichu (Pedersen et al. 2019). Na z&aacute;klade t&yacute;chto zisten&iacute; autori dospeli k z&aacute;veru, &#382;e GS-441524 je bezpe&#269;n&aacute; a &uacute;&#269;inn&aacute; lie&#269;ba FIP, ak sa pod&aacute;va v d&aacute;vke 4,0 mg\/kg BW SC jedenkr&aacute;t denne po dobu najmenej 12 t&yacute;&#382;d&#328;ov (Pedersen et al. 2019). Pre neurologick&eacute; pr&iacute;pady FIP sa odpor&uacute;&#269;ala vy&scaron;&scaron;ia d&aacute;vka 5,0 a&#382; 10,0 mg\/kg BW SC jedenkr&aacute;t denne po&#269;as 12 t&yacute;&#382;d&#328;ov, ako vyplynulo z lie&#269;by &scaron;tyroch klinick&yacute;ch pr&iacute;padov (Dickinson et al. 2020). Vzh&#318;adom na konzistenciu jej uv&aacute;dzanej &uacute;&#269;innosti vznikol narastaj&uacute;ci glob&aacute;lny &#269;ierny trh s GS-441524, preto&#382;e form&aacute;lne nebol nikde schv&aacute;len&yacute; na komer&#269;n&eacute; pou&#382;itie (Pedersen 2019b). Je zauj&iacute;mav&eacute;, &#382;e GS-441524 tie&#382; vykazoval in vitro antiv&iacute;rusov&uacute; aktivitu proti SARS-CoV (Cho et al. 2012).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Remdesivir (GS-5734), prolie&#269;ivo p&ocirc;vodn&eacute;ho anal&oacute;gu adenoz&iacute;nov&eacute;ho nukleozidu, GS-441524 (Amirian a Levy 2020), dostal  od Americk&eacute;ho &uacute;radu pre potraviny a lie&#269;iv&aacute; (FDA) povolenie na mimoriadne pou&#382;itie na lie&#269;bu podozriv&yacute;ch alebo laborat&oacute;rne potvrden&yacute;ch pr&iacute;padov COVID-19 u dospel&yacute;ch a det&iacute; hospitalizovan&yacute;ch s &#357;a&#382;kou infekciou. Toto n&uacute;dzov&eacute; schv&aacute;lenie bolo zalo&#382;en&eacute; na randomizovanej, dvojito zaslepenej, placebom kontrolovanej &scaron;t&uacute;dii uskuto&#269;nenej N&aacute;rodn&yacute;m in&scaron;tit&uacute;tom pre alergie a infek&#269;n&eacute; choroby (NIAID) (NCT04280705) a sponzorovanej otvorenej &scaron;t&uacute;dii, ktor&aacute; hodnotila r&ocirc;zne trvanie remdesiviru (NCT04292899). &#270;al&scaron;ia randomizovan&aacute;, dvojito zaslepen&aacute;, placebom kontrolovan&aacute; multicentrick&aacute; &scaron;t&uacute;dia uskuto&#269;nen&aacute; v &#268;&iacute;ne tie&#382; uk&aacute;zala, &#382;e pou&#382;itie remdesiviru u dospel&yacute;ch pacientov s COVID-19 bolo spojen&eacute; so skr&aacute;ten&iacute;m &#269;asu klinick&eacute;ho zlep&scaron;enia pri v&#269;as nasadenej lie&#269;be, hoci &scaron;tatisticky v&yacute;znamn&eacute; klinick&eacute; pr&iacute;nosy neboli pozorovan&eacute; (Wang et al. 2020). V s&uacute;&#269;asnosti v mnoh&yacute;ch krajin&aacute;ch prebiehaj&uacute; klinick&eacute; testy remdesiviru a mnoh&yacute;ch &#271;al&scaron;&iacute;ch antivirot&iacute;k na lie&#269;bu COVID-19 (Amirian a Levy 2020).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Aj ke&#271; to nes&uacute;vis&iacute; s priamou lie&#269;bou FIP, liek navrhnut&yacute; na zn&iacute;&#382;enie vylu&#269;ovania FCoV m&ocirc;&#382;e by&#357; pravdepodobn&yacute;m predchodcom prevencie FIP. Uk&aacute;zalo sa, &#382;e antiv&iacute;rusov&yacute; produkt s n&aacute;zvom Mutian&reg; X, syntetick&yacute; anal&oacute;g adenoz&iacute;nu, ktor&eacute;ho presn&eacute; zlo&#382;enie je &bdquo;obchodn&eacute; tajomstvo&ldquo;, zastavuje fek&aacute;lne vylu&#269;ovanie koronav&iacute;rusu u chronicky infikovan&yacute;ch ma&#269;iek, ke&#271; sa pod&aacute;va peror&aacute;lne v d&aacute;vke 4,0 mg\/kg telesnej hmotnosti jedenkr&aacute;t denne po&#269;as &scaron;tyroch dn&iacute; (Addie et al. 2020). Addie a kol. (2020) nazna&#269;uj&uacute;, &#382;e kombin&aacute;cia probiot&iacute;k a interfer&oacute;nu v rovnakej &scaron;t&uacute;dii viedla k zn&iacute;&#382;eniu vylu&#269;ovania koronav&iacute;rusu u dvoch ma&#269;iek. Uk&aacute;zalo sa, &#382;e ma&#269;ac&iacute; interfer&oacute;n &omega; zni&#382;uje v&iacute;rusov&eacute; vylu&#269;ovanie ma&#269;acieho koronav&iacute;rusu u ma&#269;iek infikovan&yacute;ch retrov&iacute;rusom (Gil et al. 2013).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">3.4. Ostatn&eacute; antiv&iacute;rusov&eacute; zl&uacute;&#269;eniny<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Pre svoju antiv&iacute;rusov&uacute; aktivitu proti FIPV boli testovan&eacute; aj &#271;al&scaron;ie kandid&aacute;tske zl&uacute;&#269;eniny. Napr&iacute;klad antiv&iacute;rusov&yacute; ribavir&iacute;n bol testovan&yacute; in vivo u ma&#269;iek experiment&aacute;lne infikovan&yacute;ch FIPV a bolo zisten&eacute;, &#382;e vykazuje margin&aacute;lnu antiv&iacute;rusov&uacute; aktivitu proti FIPV a toxicitu pre ma&#269;ky (Weiss et al. 1993). Bolo preuk&aacute;zan&eacute;, &#382;e cyklospor&iacute;n A, inhib&iacute;tor cyklofil&iacute;nu, inhibuje replik&aacute;ciu ma&#269;acieho koronav&iacute;rusu in vitro, aj ke&#271; mechanizmus jeho inhibi&#269;n&yacute;ch &uacute;&#269;inkov nie je zn&aacute;my (Pfefferle et al. 2011; Tanaka et al. 2012, 2013). Cyklospor&iacute;n bol pod&aacute;van&yacute; jednej ma&#269;ke s ef&uacute;znou FIP a po lie&#269;be bolo zaznamenan&eacute; zmen&scaron;enie objemu pleur&aacute;lnej tekutiny a v&iacute;rusovej n&aacute;lo&#382;e. Ma&#269;ka zomrela na respira&#269;n&eacute; zlyhanie 264. de&#328;, ale pr&iacute;&#269;ina smrti nebola stanoven&aacute; (Tanaka et al. 2015). Rovnako tak dve zl&uacute;&#269;eniny, galanthus nivalis aglutin&iacute;n (GNA) a nelfinavir (inhib&iacute;tor prote&aacute;zy), boli pri vz&aacute;jomnej kombin&aacute;cii schopn&eacute; inhibova&#357; replik&aacute;ciu FCoV in vitro (Hsieh et al. 2010). Napriek tomu sa nakoniec &#382;iadna z t&yacute;chto zl&uacute;&#269;en&iacute;n neuk&aacute;zala ako &uacute;&#269;inn&aacute;, ke&#271; sa testovala za podmienok simuluj&uacute;cich infekciu FIPV. Podobne na z&aacute;klade s&#318;ubn&yacute;ch zisten&iacute; t&yacute;kaj&uacute;cich sa &uacute;&#269;innosti inhib&iacute;torov 3C-like prote&aacute;zy proti FCoV (Kim et al. 2013, 2015, 2016) sa uskuto&#269;nila po&#318;n&aacute; &scaron;t&uacute;dia s GC376 s 20 ma&#269;kami s r&ocirc;znymi formami FIP, s v&yacute;nimkou t&yacute;ch, ktor&eacute; maj&uacute; neurologick&eacute; pr&iacute;znaky (Pedersen et al. 2018). Ma&#269;k&aacute;m bola pod&aacute;van&aacute; d&aacute;vka 15,0 mg\/kg BW, SC, dvakr&aacute;t denne, minim&aacute;lne 12 t&yacute;&#382;d&#328;ov. Aj ke&#271; v&yacute;sledky boli povzbudiv&eacute; (u siedmich ma&#269;iek sa dosiahla priemern&aacute; <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;&amp;lt;b&amp;gt;Remisia&amp;lt;\/b&amp;gt;&nbsp;je stav, ktor&yacute;m sa ozna&#269;uje zmiernenie a&#382; vymiznutie&nbsp;pr&iacute;znakov&nbsp;choroby. Opakom tohto stavu je&nbsp;relaps.&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/remisia\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">remisia<\/a> choroby 11,2 mesiaca), objavili sa ved&#318;aj&scaron;ie &uacute;&#269;inky, vr&aacute;tane prechodnej bolesti po injekcii, subkut&aacute;nnej fibr&oacute;zy, alop&eacute;cie a abnorm&aacute;lneho v&yacute;voja trval&yacute;ch zubov u ma&#269;iek lie&#269;en&yacute;ch pred 16.-18. t&yacute;&#382;d&#328;om veku (Pedersen a kol. 2018). Existuj&uacute; aj &#271;al&scaron;ie inhib&iacute;tory prote&aacute;zy cieliace na 3C-like prote&iacute;n koronav&iacute;rusov (Rathnayake a kol. 2020; Theerawatanasirikul a kol. 2020).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Antimykotick&yacute; itrakonazol preuk&aacute;zal in vitro anti-FIPV aktivitu pri n&iacute;zkych koncentr&aacute;ci&aacute;ch lie&#269;iva (2,5 &micro;M) (Takano et al. 2019). Ned&aacute;vna &scaron;t&uacute;dia in vivo sk&uacute;mala &uacute;&#269;inky kombin&aacute;cie itrakonazolu (50 mg\/zviera peror&aacute;lne, raz denne) a antihum&aacute;nnej TNF-alfa monoklon&aacute;lnej <a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;&amp;lt;!-- wp:paragraph --&amp;gt;&amp;lt;strong&amp;gt;Protil&aacute;tka&amp;lt;\/strong&amp;gt;&nbsp;(&amp;lt;strong&amp;gt;imunoglobulin&amp;lt;\/strong&amp;gt;) je&nbsp;protein, kter&yacute; je schopen jako sou&#269;&aacute;st&nbsp;imunitn&iacute;ho syst&eacute;mu&nbsp;identifikovat a zne&scaron;kodnit ciz&iacute; objekty (bakterie&nbsp;a&nbsp;viry) v t&#283;le. Protil&aacute;tky jsou nositeli&nbsp;humor&aacute;ln&iacute; imunity. Jsou to krevn&iacute; b&iacute;lkoviny vznikaj&iacute;c&iacute; v m&iacute;zn&iacute; tk&aacute;ni.&amp;lt;br\/&amp;gt;&amp;lt;!-- \/wp:paragraph --&amp;gt;&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/protilatka\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">protil&aacute;tky<\/a> (10 mg\/zviera) na lie&#269;bu troch ma&#269;iek experiment&aacute;lne infikovan&yacute;ch FIPV (Doki a kol. 2020). Aj ke&#271; dve z troch ma&#269;iek vykazovali zlep&scaron;enie klinick&yacute;ch pr&iacute;znakov s&uacute;visiacich s FIPV, po zh&aacute;jen&iacute; lie&#269;by sa zistilo zv&yacute;&scaron;enie po&#269;tu lymfocytov v perif&eacute;rnej krvi a pokles alfa-1-kysl&yacute;ch glykoprote&iacute;nov. Tretia ma&#269;ka bola utraten&aacute; z d&ocirc;vodu nereagovania na lie&#269;bu. Autori dospeli k z&aacute;veru, &#382;e t&aacute;to kombin&aacute;cia liekov m&ocirc;&#382;e by&#357; u&#382;ito&#269;n&aacute;, k&yacute;m nebud&uacute; k dispoz&iacute;cii &uacute;&#269;innej&scaron;ie l&aacute;tky proti FIPV. Itrakonazol sa v kombin&aacute;cii s prednizol&oacute;nom pou&#382;&iacute;val na lie&#269;bu ef&uacute;znej FIP u trojmesa&#269;n&eacute;ho ma&#269;iatka Scottish Fold (&Scaron;k&oacute;tska klapouch&aacute; ma&#269;ka), &#269;o viedlo k redukcii pleur&aacute;lneho v&yacute;potku (Kameshima et al. 2020). T&aacute;to ma&#269;ka v&scaron;ak vykazovala neurologick&eacute; prejavy a bola eutanizovan&aacute; kv&ocirc;li status epilepticus po 38 d&#328;och lie&#269;by (Kameshima et al. 2020). Antiv&iacute;rusov&uacute; aktivitu proti FCoV vyk&aacute;zali aj in&eacute; l&aacute;tky, vr&aacute;tane anti-ma&#269;acej TNF-alfa monoklon&aacute;lnej protil&aacute;tky (Doki et al. 2016); U18666A (inhib&iacute;tor transportu cholesterolu) (Takano et al. 2017; Doki et al. 2020); difyl&iacute;n (vakuol&aacute;rny blok&aacute;tor ATP&aacute;zy) a jeho nanoformul&aacute;cia (Hu et al. 2017) a kruhov&aacute; trojit&aacute; &scaron;pir&aacute;la tvoriaca oligonukleotidov&uacute; RNA (Choong et al. 2014). Neboli v&scaron;ak publikovan&eacute; &#382;iadne &scaron;t&uacute;die in vivo s pou&#382;it&iacute;m t&yacute;chto zl&uacute;&#269;en&iacute;n.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&#317;udsk&eacute; antimalarick&eacute; lie&#269;ivo chloroch&iacute;n tie&#382; inhibuje replik&aacute;ciu FIPV in vitro (Takano et al. 2013; McDonagh et al. 2014). O chloroch&iacute;ne je u&#382; dlho zn&aacute;me, &#382;e m&aacute; protiz&aacute;palov&eacute; a in vitro antiv&iacute;rusov&eacute; vlastnosti proti &scaron;irokej &scaron;k&aacute;le v&iacute;rusov (Takano et al. 2013). Napriek dobrej in vitro &uacute;&#269;innosti vykazoval chloroch&iacute;n slab&uacute; antiv&iacute;rusov&uacute; &uacute;&#269;innos&#357; proti in vivo experiment&aacute;lne indukovanej infekcii FIP (Takano et al. 2013). Vo svojej &scaron;t&uacute;dii Takano a kol. (2013) zistili, &#382;e lie&#269;ba chloroch&iacute;nom bola spojen&aacute; so zlep&scaron;en&iacute;m klinick&eacute;ho sk&oacute;re a mierne zv&yacute;&scaron;en&yacute;m, ale nie &scaron;tatisticky v&yacute;znamn&yacute;m &#269;asom pre&#382;itia ma&#269;iek infikovan&yacute;ch vysoko virulentn&yacute;m FCoV FIPV 1146. &#270;alej zv&yacute;&scaron;en&eacute; hladiny aktivity alan&iacute;naminotransfer&aacute;zy v skupin&aacute;ch lie&#269;en&yacute;ch chloroch&iacute;nom nazna&#269;ovali potenci&aacute;lny probl&eacute;m s po&scaron;koden&iacute;m pe&#269;ene. D&aacute;vka 10 mg\/kg telesnej hmotnosti dvakr&aacute;t t&yacute;&#382;denne SC bola extrapolovan&aacute; z protokolov d&aacute;vkovania pre &#318;ud&iacute; a nevych&aacute;dzala zo &#382;iadnych zn&aacute;mych farmakokinetick&yacute;ch &scaron;t&uacute;di&iacute; u ma&#269;iek. Antiv&iacute;rusov&aacute; aktivita hydroxychloroch&iacute;nu proti FIPV bola ned&aacute;vno tie&#382; predmetom &scaron;t&uacute;die in vitro. Ak sa hydroxychloroch&iacute;n pou&#382;il s rekombinantn&yacute;m ma&#269;ac&iacute;m IFN-&omega;, vykazoval zv&yacute;&scaron;en&uacute; antiv&iacute;rusov&uacute; aktivitu proti infekcii FIPV (Takano et al. 2020). Hydroxychloroch&iacute;n sa sk&uacute;mal aj v klinick&yacute;ch &scaron;t&uacute;di&aacute;ch na lie&#269;bu liekom COVID-19 u &#318;ud&iacute; (Lundstrom 2020). Tento liek v&scaron;ak priniesol kontroverzn&eacute; v&yacute;sledky, &#269;o viedlo k s&uacute;&#269;asn&eacute;mu z&aacute;veru, &#382;e jeho klinick&aacute; &uacute;&#269;innos&#357; u pacientov s COVID-19 nebola doposia&#318; overen&aacute; (Lundstrom 2020).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">McDonagh a kol. (2014) preverovali 19 kandid&aacute;tskych zl&uacute;&#269;en&iacute;n pou&#382;&iacute;van&yacute;ch pri lie&#269;be in&yacute;ch koronav&iacute;rusov&yacute;ch infekci&iacute; na ich bunkov&uacute; toxicitu a &uacute;&#269;innos&#357; pri inhib&iacute;cii replik&aacute;cie FIPV v infikovan&yacute;ch CRFK bunk&aacute;ch. V tejto &scaron;t&uacute;dii in vitro bol vyvinut&yacute; screeningov&yacute; test inhib&iacute;cie cytopatick&eacute;ho &uacute;&#269;inku (CPE) zalo&#382;en&yacute; na resazur&iacute;ne, aby sa zistila antiv&iacute;rusov&aacute; &uacute;&#269;innos&#357; proti dvom kme&#328;om FCoV: FECV 1683 a FIPV 1146. &#270;al&scaron;ie testy, vr&aacute;tane redukcie plaku, zn&iacute;&#382;enia vylu&#269;ovania v&iacute;rusu a viric&iacute;dnej suspenzie, boli pou&#382;it&eacute; na vyhodnotenie antiv&iacute;rusov&yacute;ch &uacute;&#269;inkov kandid&aacute;tskych zl&uacute;&#269;en&iacute;n. &Scaron;t&uacute;dia nakoniec identifikovala tri zl&uacute;&#269;eniny (chloroch&iacute;n, mefloch&iacute;n a hexametyl&eacute;n amilorid), ktor&eacute; podstatne zni&#382;ovali v&iacute;rusov&uacute; n&aacute;lo&#382; FIPV v infikovan&yacute;ch CRFK bunk&aacute;ch bez cytotoxick&yacute;ch &uacute;&#269;inkov pri koncentr&aacute;ci&aacute;ch 10 &micro;M. Predbe&#382;n&eacute; experimenty navy&scaron;e nazna&#269;uj&uacute;, &#382;e antiv&iacute;rusov&eacute; mechanizmy v&scaron;etk&yacute;ch troch zl&uacute;&#269;en&iacute;n p&ocirc;sobia v po&#269;iato&#269;nom &scaron;t&aacute;diu v&iacute;rusovej replik&aacute;cie.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Vzh&#318;adom na potenci&aacute;lny vplyv t&yacute;chto v&yacute;sledkov na lie&#269;bu FIP je potrebn&eacute; &#271;al&scaron;ie sk&uacute;manie t&yacute;chto zl&uacute;&#269;en&iacute;n (McDonagh et al. 2014). Chloroch&iacute;n aj mefloch&iacute;n s&uacute; komer&#269;ne dostupn&eacute; farmaceutick&eacute; l&aacute;tky registrovan&eacute; pre pou&#382;itie u &#318;ud&iacute;. Za ka&#382;d&yacute;m z nich je mno&#382;stvo podpornej literat&uacute;ry t&yacute;kaj&uacute;cej sa ich farmakokinetiky a bezpe&#269;nosti u in&yacute;ch ako ma&#269;kovit&yacute;ch druhov. Niektor&eacute; inform&aacute;cie o farmakokinetickom profile mefloch&iacute;nu u ma&#269;iek u&#382; s&uacute; k dispoz&iacute;cii (Izes 2019; Izes et al. 2020a, 2019, 2020b; Yu et al. 2020). O hexametyl&eacute;n amiloride sa vie podstatne menej, najm&auml; s oh&#318;adom na jeho bezpe&#269;nos&#357; (McDonagh et al. 2014). Ke&#271;&#382;e Takano a kol. (2013), ktor&iacute; predt&yacute;m spochybnili in vivo &uacute;&#269;innos&#357; chloroch&iacute;nu proti FIP, stoja za &uacute;vahu klinick&eacute; testy mefloch&iacute;nu na lie&#269;bu infikovan&yacute;ch ma&#269;iek. Posledn&eacute; farmakokinetick&eacute; &scaron;t&uacute;die in vitro nazna&#269;ili, &#382;e mefloch&iacute;n prech&aacute;dza pe&#269;e&#328;ov&yacute;m metabolizmom f&aacute;zy I, ale nie glukuronidat&iacute;vnym metabolizmom f&aacute;zy II, ak je katalyzovan&yacute; ma&#269;ac&iacute;mi pe&#269;e&#328;ov&yacute;mi mikroz&oacute;mami, a preto nie je pravdepodobn&eacute;, &#382;e by sp&ocirc;sobil u ma&#269;iek oneskoren&uacute; elimin&aacute;ciu (Izes et al. 2020a). Farmakokinetick&yacute; profil mefloch&iacute;nu u ma&#269;iek bol sk&uacute;man&yacute; v o&#269;ak&aacute;van&iacute; uskuto&#269;nenia klinick&yacute;ch &scaron;t&uacute;di&iacute; na inhib&iacute;ciu ma&#269;acieho koronav&iacute;rusu a ma&#269;acieho kaliciv&iacute;rusu u ma&#269;iek klinicky postihnut&yacute;ch t&yacute;mito v&iacute;rusov&yacute;mi infekciami (Yu et al. 2020). Prebiehaj&uacute; &#271;al&scaron;ie v&yacute;skumy klinickej &uacute;&#269;innosti mefloch&iacute;nu u ma&#269;iek s potvrdenou FIP.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">S oh&#318;adom na v&scaron;etky uveden&eacute; antiv&iacute;rusov&eacute; l&aacute;tky, je d&ocirc;le&#382;it&eacute; poznamena&#357;, &#382;e m&ocirc;&#382;e by&#357; nutn&eacute; pod&aacute;va&#357; kombin&aacute;ciu terapeut&iacute;k, aby sa inhibovala selekcia v&iacute;rusovej rezistencie v monoterapii.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">4. Z&aacute;ver<\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Napriek absencii ich komer&#269;nej dostupnosti, sa antiv&iacute;rusov&eacute; l&aacute;tky ako GS-441524 a GC376 uk&aacute;zali ako &uacute;&#269;inn&eacute; mo&#382;nosti lie&#269;by FIP. Zatia&#318; &#269;o sa &#269;ak&aacute; na schv&aacute;lenie t&yacute;chto l&aacute;tok, je potrebn&eacute; d&ocirc;kladnej&scaron;ie presk&uacute;ma&#357; &#271;al&scaron;ie komer&#269;ne dostupn&eacute; l&aacute;tky, ako napr&iacute;klad mefloch&iacute;n a itrakonazol, &scaron;t&uacute;diami in vivo, aby sa zistil ich skuto&#269;n&yacute; potenci&aacute;l ako antivirot&iacute;k pre lie&#269;bu FIPV. Navy&scaron;e, zatia&#318; &#269;o s&uacute;&#269;asn&aacute; pand&eacute;mia SARS-CoV-2 predstavovala pre veterin&aacute;rnu medic&iacute;nu len mal&yacute; pr&iacute;nos, glob&aacute;lny pr&iacute;stup One Health n&aacute;m hovor&iacute;, &#382;e je potrebn&eacute; sledova&#357; terapeutick&yacute; pokrok v boji proti koronav&iacute;rusom, preto&#382;e inform&aacute;cie m&ocirc;&#382;u by&#357; nakoniec u&#382;ito&#269;n&eacute; medzi druhmi.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span style=\"color: #cf2e2e;\" class=\"ugb-highlight\">Literat&uacute;ra<\/span><\/h2>\n\n\n\n<ol class=\"lm-ul-small wp-block-list\"><li>Addie D, Bel&aacute;k S, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Hosie MJ, Lloret A, Lutz H, et al. . 2009.&nbsp;Feline infectious peritonitis. 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Izes, Jane Yu, Jacqueline M. Norris, and Merran Govendir ? A summary of treatment options and medications that have emerged from years of research into this dreaded disease.<\/p>","protected":false},"author":1,"featured_media":4695,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_uag_custom_page_level_css":"","footnotes":""},"categories":[187,188],"tags":[],"class_list":["post-4691","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-odborne","category-preverejnost"],"featured_image_urls_v2":{"full":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD.jpg",1920,1080,false],"thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-150x150.jpg",150,150,true],"medium":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-300x169.jpg",300,169,true],"medium_large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-768x432.jpg",525,295,true],"large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-1024x576.jpg",525,295,true],"1536x1536":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-1536x864.jpg",1536,864,true],"2048x2048":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD.jpg",1920,1080,false],"trp-custom-language-flag":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-16x9.jpg",16,9,true],"twentyseventeen-featured-image":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD.jpg",1920,1080,false],"twentyseventeen-thumbnail-avatar":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-100x100.jpg",100,100,true],"woocommerce_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-250x250.jpg",250,250,true],"woocommerce_single":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-350x197.jpg",350,197,true],"woocommerce_gallery_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD-100x100.jpg",100,100,true]},"post_excerpt_stackable_v2":"<p>Aaron M. Izes, Jane Yu, Jacqueline M. Norris, and Merran Govendir  ? Zhrnutie mo&#382;nost&iacute; lie&#269;by a liekov, ktor&eacute; vyplynuli z dlhoro&#269;n&eacute;ho v&yacute;skumu tejto ob&aacute;vanej choroby.<\/p>\n","category_list_v2":"<a href=\"https:\/\/www.fipwarriors.eu\/en\/category\/odborne\/\" rel=\"category tag\">Odborn\u00e9<\/a>, <a href=\"https:\/\/www.fipwarriors.eu\/en\/category\/preverejnost\/\" rel=\"category tag\">Pre verejnos\u0165<\/a>","author_info_v2":{"name":"LM","url":"https:\/\/www.fipwarriors.eu\/en\/author\/starman\/"},"comments_num_v2":"0 comments","featured_image_src":"https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/close-up-of-cat-lying-on-floor-at-homeFHD.jpg","author_info":{"display_name":"L. M.","author_link":"https:\/\/www.fipwarriors.eu\/en\/author\/starman\/"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Aktu\u00e1lne mo\u017enosti lie\u010dby ma\u010diek s FIP a ma\u010diek pozit\u00edvnych na SARS-CoV-2 - FIP Warriors CZ\/SK \u00ae<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.fipwarriors.eu\/en\/aktualny-stav-moznosti-liecby-fip-a-maciek-pozitivnych-na-sars-cov-2\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Aktu\u00e1lne mo\u017enosti lie\u010dby ma\u010diek s FIP a ma\u010diek pozit\u00edvnych na SARS-CoV-2 - FIP Warriors CZ\/SK \u00ae\" \/>\n<meta property=\"og:description\" content=\"Aaron M. Izes, Jane Yu, Jacqueline M. 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