{"id":2257,"date":"2021-09-20T08:41:05","date_gmt":"2021-09-20T06:41:05","guid":{"rendered":"https:\/\/www.newslab.sk\/genomicka-variabilita-virusu-sars-cov-2\/"},"modified":"2021-09-20T08:48:23","modified_gmt":"2021-09-20T06:48:23","slug":"genomic-variability-of-sars-cov-2","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/genomic-variability-of-sars-cov-2\/","title":{"rendered":"Genomic variability of SARS-CoV-2"},"content":{"rendered":"

*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens<\/strong><\/span><\/p>\n

<\/h3>\n

Varianty v\u00edrusu SARS-CoV-2<\/strong><\/h3>\n

Mut\u00e1cie s\u00fa jeden z najd\u00f4le\u017eitej\u0161\u00edch mechanizmov evol\u00facie RNA v\u00edrusov. Podobne ako in\u00e9 RNA v\u00edrusy, aj koronav\u00edrusy rutinne akumuluj\u00fa mut\u00e1cie a zmeny vo svojej gen\u00f3movej sekvencii v d\u00f4sledku nepresnosti polymer\u00e1zy(1<\/a>). SARS-CoV-2 v\u0161ak obsahuje RdRp s proof-reading <\/em>aktivitou, ktor\u00e1 m\u00e1 za \u00falohu minimalizova\u0165 v\u00fdskyt nukleotidov\u00fdch mut\u00e1ci\u00ed(2<\/a>). Genetick\u00e1 diverzita je v\u0161ak rozhoduj\u00faca pre jeho fitnes, pre\u017eitie aj patogen\u00e9zu. Bolo vykonan\u00e9 ve\u013ek\u00e9 mno\u017estvo \u0161t\u00fadi\u00ed na detekciu gen\u00f3mov\u00fdch vari\u00e1ci\u00ed SARS-CoV-2, \u010do viedlo k n\u00e1jdeniu bohat\u00fdch genetick\u00fdch vari\u00e1ci\u00ed r\u00f4znych typov vr\u00e1tane nesynonymn\u00fdch, synonymn\u00fdch, inzerci\u00ed, del\u00e9ci\u00ed a nek\u00f3duj\u00facich mut\u00e1ci\u00ed. Monitorovanie (obr\u00e1zok 1) <\/strong>a charakteriz\u00e1cia mut\u00e1ci\u00ed a variabiln\u00fdch oblast\u00ed je rozhoduj\u00faca najm\u00e4 pre ich d\u00f4sledky, ako napr\u00edklad vplyv na r\u00fdchlos\u0165 \u0161\u00edrenia infekcie alebo schopnos\u0165 sp\u00f4sobi\u0165 v\u00e1\u017enej\u0161\u00ed priebeh ochorenia.<\/p>\n

Mut\u00e1cie m\u00f4\u017eu sp\u00f4sobova\u0165 neschopnos\u0165 detekcie v\u00edrusu pomocou \u0161pecifick\u00fdch diagnostick\u00fdch testov alebo zn\u00ed\u017ei\u0165 n\u00e1chylnos\u0165 na terapeutick\u00e9 l\u00e1tky, ako s\u00fa monoklon\u00e1lne protil\u00e1tky, \u010di vyhn\u00fa\u0165 sa prirodzenej imunite alebo imunite vyvolanej o\u010dkovan\u00edm. S najv\u00e4\u010d\u0161ou pravdepodobnos\u0165ou sa bud\u00fa pren\u00e1\u0161a\u0165 mut\u00e1cie, ktor\u00e9 bu\u010f posilnia infek\u010dnos\u0165, alebo replik\u00e1ciu v\u00edrusu, alebo tie, ktor\u00e9 nevpl\u00fdvaj\u00fa negat\u00edvne na funkciu v\u00edrusu. Ke\u010f\u017ee sa zv\u00fd\u0161il prenos a glob\u00e1lne \u0161\u00edrenie SARS-CoV-2, v s\u00fa\u010dasnosti pozorujeme ve\u013ek\u00e9 mno\u017estvo akumulovan\u00fdch mut\u00e1ci\u00ed. Pod\u013ea \u00fadajov z\u00edskan\u00fdch z verejnej datab\u00e1zy Global Initiative on Sharing All Influenza Data (GISAID) mal na za\u010diatku pand\u00e9mie v\u00edrus SARS-CoV-2 mieru mut\u00e1ci\u00ed asi 1,12 x 10\u20133 nukleotidov\/gen\u00f3m za rok(3<\/a>). Zatia\u013e \u010do sekvencie SARS-CoV-2 z Wu-chanu a okolit\u00fdch oblast\u00ed provincie Chu-pej sa l\u00ed\u0161ili iba nieko\u013ek\u00fdmi nukleotidov\u00fdmi zmenami, \u010fal\u0161ia anal\u00fdza gen\u00f3mov\u00fdch sekvenci\u00ed z datab\u00e1zy GISAID odhalila, \u017ee po\u010det a v\u00fdskyt mut\u00e1ci\u00ed je v Eur\u00f3pe a Severnej Amerike v porovnan\u00ed s \u00c1ziou v\u00fdrazne vy\u0161\u0161\u00ed(4<\/a>). Napriek tomu, \u017ee SARS-CoV-2 vykazuje sez\u00f3nny pokles, perzistencia pand\u00e9mie m\u00f4\u017ee umo\u017eni\u0165 akumul\u00e1ciu imunologicky relevantn\u00fdch mut\u00e1ci\u00ed v popul\u00e1cii. Prote\u00edny SARS-CoV-2 mutuj\u00fa r\u00f4znymi r\u00fdchlos\u0165ami, pri\u010dom v\u00e4\u010d\u0161ina v\u00edrusov\u00fdch prote\u00ednov vykazuje mal\u00fa muta\u010dn\u00fa variabilitu. Niektor\u00e9 prote\u00edny, ako napr\u00edklad Spike, sa zdaj\u00fa n\u00e1chylnej\u0161ie na mut\u00e1cie, pravdepodobne pre svoju k\u013e\u00fa\u010dov\u00fa \u00falohu pri vstupe do hostite\u013esk\u00fdch buniek a zmenu infek\u010dnosti(5<\/a>).<\/p>\n

V\u00fdznamn\u00fa pozornos\u0165 z\u00edskala mut\u00e1cia D614G v S prote\u00edne, ke\u010f\u017ee sa stala v polovici roku 2020 prevl\u00e1daj\u00facou formou SARS-CoV-2 na celom svete vr\u00e1tane Eur\u00f3py. Ide o substit\u00faciu ved\u00facu k nahradeniu kyseliny aspar\u00e1govej glyc\u00ednom v polohe 614 v S prote\u00edne(7<\/a>). Doteraz nie s\u00fa d\u00f4kazy o tom, \u017ee by infekcia SARS-CoV-2 obsahuj\u00faca tento variant viedla k z\u00e1va\u017enej\u0161iemu priebehu ochorenia a nemen\u00ed ani \u00fa\u010dinnos\u0165 existuj\u00facich laborat\u00f3rnych diagnost\u00edk, terapeut\u00edk, vakc\u00edn alebo prevent\u00edvnych opatren\u00ed v oblasti verejn\u00e9ho zdravia. Mut\u00e1cia v\u0161ak pravdepodobne zv\u00fd\u0161ila afinitu v\u00edrusu na \u013eudsk\u00fd receptor ACE2, \u010do m\u00e1 za n\u00e1sledok jeho vy\u0161\u0161iu infek\u010dnos\u0165 a r\u00fdchlos\u0165 prenosu(8<\/a>). Je preuk\u00e1zan\u00e9, \u017ee infikovan\u00ed pacienti s D614G mali vy\u0161\u0161iu hladinu v\u00edrusovej RNA, nezistili sa v\u0161ak rozdiely v potrebe hospitaliz\u00e1cie(7<\/a>). \u010eal\u0161ia be\u017en\u00e1 mut\u00e1cia v polohe 314 v ORF1b ovplyv\u0148uje komplex RdRp, ktor\u00fd je k\u00f3dovan\u00fd nsp12. Mut\u00e1cie v RdRp s\u00fa zriedka \u017eivotaschopn\u00e9, preto\u017ee RdRp je zodpovedn\u00fd za transkrip\u010dn\u00e9 procesy a jeho \u0161trukt\u00fara je preto vysoko zachov\u00e1van\u00e1. Mut\u00e1cia vedie k zmene aminokyseliny prol\u00edn na leuc\u00edn a bolo pozorovan\u00e9, \u017ee zvy\u0161uje r\u00fdchlos\u0165 v\u00fdskytu mut\u00e1ci\u00ed(9<\/a>). Prol\u00edn je spojen\u00fd s flexibilitou a leuc\u00edn so stabiliz\u00e1ciou v prote\u00ednoch. Zv\u00fd\u0161en\u00e1 rigidita v \u0161trukt\u00fare RdRp v d\u00f4sledku zavedenia leuc\u00ednu vedie k vy\u0161\u0161ej miere transkrip\u010dnej chyby(10<\/a>). Vznik mut\u00e1cie RdRp vo febru\u00e1ri 2020 viedol k zv\u00fd\u0161eniu tvorby mut\u00e1ci\u00ed vr\u00e1tane mut\u00e1ci\u00ed v S a N prote\u00ednoch(4<\/a>).<\/p>\n

Na konci jesene 2020 viacer\u00e9 krajiny hl\u00e1sili, \u017ee deteguj\u00fa varianty SARS-CoV-2 s ve\u013ek\u00fdm po\u010dtom mut\u00e1ci\u00ed, ktor\u00e9 sa \u0161\u00edria efekt\u00edvnej\u0161ie. Nov\u00fd variant B.1. 1. 7 s ve\u013ek\u00fdm po\u010dtom mut\u00e1ci\u00ed identifikovali na jese\u0148 2020 v Brit\u00e1nii(11)<\/a>. N\u00e1sledne bola ohl\u00e1sen\u00e1 l\u00ednia B.1.351 v Ju\u017enej Afrike(12<\/a>). Ned\u00e1vno boli identifikovan\u00e9 \u010fal\u0161ie varianty, a to B.1. 1. 28 ozna\u010dovan\u00fd ako P.1 v Braz\u00edlii(13<\/a>) a B.1.526 vyskytuj\u00faci sa najm\u00e4 v New Yorku(14<\/a>). V s\u00fa\u010dasnosti tieto varianty SARS-CoV-2 predstavuj\u00fa najv\u00e4\u010d\u0161iu hrozbu. O funk\u010dn\u00fdch a evolu\u010dn\u00fdch v\u00fdznamoch v\u00e4\u010d\u0161iny mut\u00e1ci\u00ed SARS CoV-2 sa st\u00e1le diskutuje.<\/p>\n

 <\/p>\n

L\u00ednia B.1.1.7<\/h3>\n

B.1. 1. 7 rodov\u00e1 l\u00ednia, alias 20I\/501Y.V1 Variant of Concern (VOC) 202012\/01. Patr\u00ed do skupiny Nextstrain \u2013 20 B, GISAID klad GR. Rodov\u00e1 l\u00ednia B.1. 1. 7 nesie v\u00e4\u010d\u0161\u00ed po\u010det genetick\u00fdch zmien v\u00edrusu, ako bolo obvykl\u00e9(11<\/a>). Ako a kde vznikol, je zatia\u013e nejasn\u00e9. Predpokladan\u00fd vznik neobvyklej genetickej divergencie l\u00ednie B.1. 1. 7 je v imunodeficientn\u00fdch alebo imunosuprimovan\u00fdch pacientoch, ktor\u00ed s\u00fa chronicky infikovan\u00ed SARS-CoV-2(15<\/a>). V tak\u00fdchto pr\u00edpadoch evolu\u010dn\u00e1 dynamika a selekt\u00edvne tlaky na popul\u00e1ciu v\u00edrusov medzi pacientmi s\u00fa ve\u013emi odli\u0161n\u00e9 od t\u00fdch, ktor\u00e9 sa vyskytuj\u00fa pri typickej infekcii. Odhaduje sa, \u017ee variant sa objavil v juhov\u00fdchodnej \u010dasti Ve\u013ekej Brit\u00e1nie v septembri 2020, pri\u010dom nie je fylogeneticky pr\u00edbuzn\u00fd s v\u00edrusom SARS-CoV-2 cirkuluj\u00facim v Spojenom kr\u00e1\u013eovstve v \u010dase zistenia variantu(16<\/a>).<\/p>\n

Nukleotidov\u00e9 zmeny s\u00fa preva\u017ene pozme\u0148uj\u00face aminokyseliny, pri\u010dom nastalo a\u017e 14 nesynonymn\u00fdch mut\u00e1ci\u00ed a 3 del\u00e9cie (obr\u00e1zok 2)<\/strong>. V l\u00ednii sa pozoruje aj 6 synonymn\u00fdch mut\u00e1ci\u00ed. Mno\u017estvo genetick\u00fdch zmien je najm\u00e4 v prote\u00edne Spike vr\u00e1tane del\u00e9cie \u0161iestich nukleotidov, \u010do vedie k del\u00e9cii 2 aminokysel\u00edn v poz\u00edci\u00e1ch 69 a 70 \u2013 del69\u201370. T\u00e1to mut\u00e1cia sa spont\u00e1nne vyvinula aj v in\u00fdch variantoch SARS-CoV-2 a pred- poklad\u00e1 sa, \u017ee zvy\u0161uje prenosnos\u0165. V\u00fdznamnou mut\u00e1ciou je aj zmena, ktor\u00e1 vedie k zmene aminokyseliny z asparag\u00ednu na tyroz\u00edn v polohe 501 \u2013 N501Y v dom\u00e9ne via\u017eucej receptor prote\u00ednu Spike. Uk\u00e1zalo sa, \u017ee zvy\u0161uje pevnos\u0165 v\u00e4zby Spike prote\u00ednu koronav\u00edrusu na enz\u00fdm konvertuj\u00faci angiotenz\u00edn 2 \u2013 ACE2, ktor\u00fd sprostredk\u00fava vstup v\u00edrusu do \u013eudsk\u00fdch buniek. Potenci\u00e1lne biologick\u00e9 \u00fa\u010dinky m\u00f4\u017ee ma\u0165 aj zmena prol\u00ednu na aminokyselinu histid\u00ednu v polohe 681 v S prote\u00edne \u2013 P681H, ktor\u00e1 bezprostredne sused\u00ed s miestom \u0161tiepenia fur\u00ednom(11<\/a>).<\/p>\n

Doteraj\u0161ie anal\u00fdzy uk\u00e1zali, \u017ee variant B.1. 1. 7 sa pren\u00e1\u0161a efekt\u00edvnej\u0161ie v porovnan\u00ed s in\u00fdmi variantmi SARS-CoV-2, ktor\u00e9 koluj\u00fa vo Ve\u013ekej Brit\u00e1nii, ke\u010f\u017ee regi\u00f3ny Spojen\u00e9ho kr\u00e1\u013eovstva s vy\u0161\u0161\u00edm podielom sekvenci\u00ed B.1. 1. 7 mali r\u00fdchlej\u0161\u00ed epidemick\u00fd rast ako in\u00e9 oblasti. Odhaduje sa, \u017ee prenosnos\u0165 tohto kme\u0148a sa mohla zv\u00fd\u0161i\u0165 a\u017e o 56 % a prim\u00e1rne reproduk\u010dn\u00e9 \u010d\u00edslo \u0161\u00edrenia sa zv\u00fd\u0161ilo o 0,4 \u2013 0,7(17<\/a>). V janu\u00e1ri 2021 bola publikovan\u00e1 spr\u00e1va, v ktorej vedci nazna\u010dili, \u017ee variant B.1. 1. 7 m\u00f4\u017ee by\u0165 spojen\u00fd so zv\u00fd\u0161en\u00fdm rizikom \u00famrtia v porovnan\u00ed s in\u00fdmi variantmi(18<\/a>). Na potvrdenie tohto zistenia s\u00fa potrebn\u00e9 \u010fal\u0161ie \u0161t\u00fadie. Po\u010das posledn\u00fdch t\u00fd\u017ed\u0148ov pomer pr\u00edpadov B.1. 1. 7 medzi v\u0161etk\u00fdmi detegovan\u00fdmi pr\u00edpadmi v\u00fdrazne st\u00fapa ka\u017ed\u00fd de\u0148, \u010do nazna\u010duje, \u017ee tento variant sa st\u00e1va dominantn\u00fdm, minim\u00e1lne v E\u00da vr\u00e1tane Slovenska.<\/p>\n

Uk\u00e1zalo sa, \u017ee sa vyskytol aj variant B.1. 1. 7, ktor\u00fd obsahoval navy\u0161e v\u00fdznamn\u00fa mut\u00e1ciu E484K, pri ktorej sa preuk\u00e1zalo, \u017ee redukuje neutraliz\u00e1ciu rekonvalescentn\u00fdmi s\u00e9rami a monoklon\u00e1lnymi protil\u00e1tkami. Ide o klaster s ozna\u010den\u00edm VOC 202102\/02 a obsahuje v\u0161etky mut\u00e1cie op\u00edsan\u00e9 pre l\u00edniu B.1. 1. 7 s \u010fal\u0161\u00edmi mut\u00e1ciami E484K v S prote\u00edne, L730F v ORF1ab aj A173V a A398T v prote\u00edne N. Nez\u00e1visl\u00e9 \u0161t\u00fadie dospeli k z\u00e1veru, \u017ee E484K najm\u00e4 v kombin\u00e1cii s N501Y m\u00e1 medzi jednotliv\u00fdmi mut\u00e1ciami najv\u00e4\u010d\u0161\u00ed vplyv na antig\u00e9nne zmeny a je spojen\u00fd aj so zv\u00fd\u0161enou v\u00e4zbou na \u013eudsk\u00fd ACE2. Mut\u00e1cia E484K bola nez\u00e1visle op\u00edsan\u00e1 vo viacer\u00fdch variantoch vr\u00e1tane B.1.351 v Ju\u017enej Afrike, ale aj pri variante P1 v Braz\u00edlii(19<\/a>).<\/p>\n

 <\/p>\n

L\u00ednia B 1.351<\/h3>\n

B.1.351 rodov\u00e1 l\u00ednia, zn\u00e1ma ako 20H\/501Y.V2 (predt\u00fdm 20C\/501Y.V2), VOC \u2013 202012\/02 patr\u00ed do triedy Nextstrain \u2013 20C, GISAID klad GH a l\u00ednia PANGO B.1.351. Podobne ako predch\u00e1dzaj\u00faca B1. 1. 7 patr\u00ed k l\u00edni\u00e1m s ve\u013ek\u00fdm mno\u017estvom mut\u00e1ci\u00ed (obr\u00e1zok 3)<\/strong>, pri\u010dom prv\u00fdkr\u00e1t bola op\u00edsan\u00e1 v okt\u00f3bri v Ju\u017enej Afrike(12)<\/a>. Variant je definovan\u00fd viacer\u00fdmi nesynonymn\u00fdmi aminokyselinov\u00fdmi z\u00e1menami v S prote\u00edne. Napr\u00edklad v N-koncovej dom\u00e9ne S prote\u00ednu sa nach\u00e1dza del\u00e9cia 242-244del a aminokyselinov\u00e1 z\u00e1mena argin\u00ednu za izoleuc\u00edn \u2013 R246I. V RBD sa vyskytuj\u00fa tri mut\u00e1cie K417N, E484K a N501Y a jedna mut\u00e1cia A701V je lokalizovan\u00e1 v bl\u00edzkosti miesta \u0161tiepenia fur\u00ednom (12<\/a>). Mut\u00e1cia N501Y, ktor\u00e1 je rovnak\u00e1 aj v pr\u00edpade variantu B.1. 1. 7, pravdepodobne sp\u00f4sobuje zv\u00fd\u0161en\u00fa v\u00edrusov\u00fa z\u00e1\u0165a\u017e, a teda aj prenosnos\u0165 obidvoch variantov. Obzvl\u00e1\u0161\u0165 d\u00f4le\u017eit\u00e1 je mut\u00e1cia E484K v RBD, ktor\u00e1 je pova\u017eovan\u00e1 za mut\u00e1ciu, ktorej v\u00fdsledkom je schopnos\u0165 vyhn\u00fa\u0165 sa monoklon\u00e1lnym a s\u00e9rov\u00fdm protil\u00e1tkov\u00fdm odpovediam. Viac ako 90 % pr\u00edpadov sekvenovan\u00fdch v Ju\u017enej Afrike od konca novembra bolo sp\u00f4soben\u00fdch t\u00fdmto variantom(12<\/a>). Infekcie t\u00fdmto variantom boli ned\u00e1vno hl\u00e1sen\u00e9 z Rak\u00faska a r\u00fdchly n\u00e1rast pr\u00edpadov je pozorovan\u00fd aj vo Franc\u00fazsku(21<\/a>). Prv\u00e9 sporadick\u00e9 pr\u00edpady s\u00fa zachyten\u00e9 aj na Slovensku.<\/p>\n

 <\/p>\n

L\u00ednia P1<\/h3>\n

L\u00ednia P.1, zn\u00e1ma ako 20 J\/501Y.V3, patr\u00ed do triedy Nextstrain \u2013 20 B, GISAID klad GR a l\u00ednia PANGO P.1. D\u0148a 12. janu\u00e1ra 2021 bol definovan\u00fd \u010fal\u0161\u00ed variant SARS-CoV-2 v severnej Braz\u00edlii. L\u00edniu P.1 definuje 17 aminokyselinov\u00fdch zmien, 3 del\u00e9cie, 4 synonymn\u00e9 mut\u00e1cie a jedna 4-nukleotidov\u00e1 inzercia (obr\u00e1zok 4)<\/strong>. Z tohto po\u010dtu sa 10 mut\u00e1ci\u00ed nach\u00e1dza v S prote\u00edne. M\u00e1 v\u0161ak mno\u017estvo jedine\u010dn\u00fdch mut\u00e1ci\u00ed definuj\u00facich l\u00edniu vr\u00e1tane nieko\u013ek\u00fdch toto\u017en\u00fdch mut\u00e1ci\u00ed s l\u00edniou B. 1.351 zn\u00e1meho biologick\u00e9ho v\u00fdznamu, ako s\u00fa E484K, K417T a N501Y(13<\/a>).<\/p>\n

 <\/p>\n

L\u00ednia B.1.526<\/h3>\n

L\u00ednia B.1.526 patr\u00ed do triedy Nextstrain \u2013 20C a l\u00ednia PAN- GO B.1.526. Anal\u00fdza sekvenci\u00ed v\u00edrusu ned\u00e1vno identifikovala nov\u00fd variant B.1.526, ktor\u00fd sa ve\u013emi r\u00fdchlo roz\u0161\u00edril v oblasti New Yorku. L\u00ednia m\u00e1 p\u00e4\u0165 charakteristick\u00fdch aminokyselinov\u00fdch substit\u00faci\u00ed v Spike prote\u00edne L5F, T95I, D253G, D614G a A701V. Mut\u00e1cia D253G nastala pr\u00e1ve v jednom z dvoch k\u013e\u00fa\u010dov\u00fdch zvy\u0161kov N-termin\u00e1lnej dom\u00e9ny Spike prote\u00ednu. V druhom aminokyselinovom zvy\u0161ku R246 sa pozorovala mut\u00e1cia v l\u00ednii B.1.351, ktor\u00e1 pravdepodobne prispela k \u00faniku pred neutraliza\u010dn\u00fdmi protil\u00e1tkami. Predpoklad\u00e1 sa, \u017ee mut\u00e1cia D253G m\u00f4\u017ee ma\u0165 podobn\u00fd efekt(14<\/a>). Navy\u0161e boli identifikovan\u00e9 dve verzie variantu s mut\u00e1ciou E484K alebo S477N vo v\u00e4zbovej dom\u00e9ne pre receptor. Pr\u00e1ve s kombin\u00e1ciou mut\u00e1cie D253G vyvol\u00e1vaj\u00fa obavy z mo\u017enej rezistencie proti terapeutick\u00fdm a vakc\u00ednami vyvolan\u00fdm protil\u00e1tkam(22<\/a>).<\/p>\n

 <\/p>\n

L\u00ednia B.1.617<\/h3>\n

S\u00fa\u010dasn\u00fd (datovan\u00e9 k apr\u00edlu 2021) drastick\u00fd n\u00e1rast po\u010dtu pr\u00edpadov na ochorenie COVID-19 je zapr\u00ed\u010dinen\u00fd z ve\u013ekej \u010dasti l\u00edniou B.1.617. T\u00e1to mut\u00e1cia sa vyskytuje najm\u00e4 v Indii a je ozna\u010dovan\u00e1 ako \u201edvojit\u00e1 mut\u00e1cia\u201c, ke\u010f\u017ee okrem l\u00edni\u00ed charakteristick\u00fdch mut\u00e1ci\u00ed sa v RBD Spike prote\u00ednu nach\u00e1dzaj\u00fa dve v\u00fdznamn\u00e9 aminokyselinov\u00e9 substit\u00facie E484Q a L452R, ktor\u00e9 boli detegovan\u00e9 vo dvoch zn\u00e1mych l\u00edni\u00e1ch(23<\/a>). Obe mut\u00e1cie maj\u00fa zv\u00fd\u0161en\u00fa pevnos\u0165 v\u00e4zby na ACE2 receptory(24<\/a>). Vedci sa ob\u00e1vaj\u00fa, \u017ee pr\u00e1ve l\u00ednia B1.617 by mohla zv\u00fd\u0161i\u0165 pravdepodobnos\u0165 reinfekci\u00ed.<\/p>\n

 <\/p>\n

Z\u00e1ver<\/span><\/h3>\n

Vo viacer\u00fdch zn\u00e1mych l\u00edni\u00e1ch m\u00f4\u017eeme pozorova\u0165 prel\u00ednanie rovnak\u00fdch mut\u00e1ci\u00ed. Napr\u00edklad mut\u00e1cia E484K je pozorovan\u00e1 v l\u00edni\u00e1ch P.1, B.1.351 a B.1.525. V l\u00edni\u00e1ch B.1. 1. 7,<\/p>\n

B.1.351 aj P1 sa vyskytuj\u00fa mut\u00e1cie N501Y a del\u00e9cia ORF1b del11288\u201311296. S\u00fabor mut\u00e1ci\u00ed \u010di del\u00e9ci\u00ed medzi l\u00edniami sa v\u0161ak jav\u00ed ako \u00faplne samostatn\u00fd a predpoklad\u00e1 sa, \u017ee s\u00favis\u00ed s r\u00fdchlym n\u00e1rastom pr\u00edpadov v lokalit\u00e1ch v\u00fdskytu. Vzh\u013eadom na s\u00fa\u010dasn\u00fa situ\u00e1ciu je preto nevyhnutn\u00e9 v\u00edrus na\u010falej sk\u00fama\u0165 a odha\u013eova\u0165 pr\u00edpadn\u00e9 nov\u00e9 l\u00ednie v\u00edrusu. Na z\u00e1klade sekven\u010dn\u00fdch anal\u00fdz odha\u013euj\u00facich muta\u010dn\u00e9 spr\u00e1vanie v\u00edrusu SARS-CoV-2 existuj\u00fa ur\u010dit\u00e9 obavy t\u00fdkaj\u00face sa st\u00e1le novoobjavuj\u00facich sa mut\u00e1ci\u00ed, ktor\u00e9 m\u00f4\u017eu v\u00fdznamne ovplyvni\u0165 cielen\u00e9 terapie a, \u010do je d\u00f4le\u017eitej\u0161ie, pr\u00e1ve v\u00fdvoj vakc\u00edn. Preto ve\u013ek\u00e1 \u010das\u0165 vedeckej komunity upriamila pozornos\u0165 na pochopenie v\u00edrusu, ke\u010f\u017ee pr\u00e1ve v\u00fdvoj \u00fa\u010dinnej a bezpe\u010dnej vakc\u00edny m\u00f4\u017ee zabr\u00e1ni\u0165 z\u00e1va\u017enosti ochorenia a zn\u00ed\u017ei\u0165 \u00famrtnos\u0165 spojen\u00fa s t\u00fdmto ochoren\u00edm.<\/p>\n

 <\/p>\n

Po\u010fakovanie<\/em><\/strong><\/p>\n

T\u00e1to publik\u00e1cia vznikla v\u010faka podpore v r\u00e1mci opera\u010dn\u00e9ho programu Integrovan\u00e1 infra\u0161trukt\u00fara ITMS:313011ATL7, ktor\u00fd je spolufinancovan\u00fd zo zdrojov Eur\u00f3pskeho fondu region\u00e1lneho rozvoja a s podporou Agent\u00fary na podporu v\u00fdskumu a v\u00fdvoja na z\u00e1klade Zmluvy \u010d. PP-COVID-20-0051.<\/em><\/p>\n

 <\/p>\n

LITERAT\u00daRA<\/strong><\/p>\n

    \n
  1. Sanju\u00e1n R, Nebot MR, Chirico N, et al. Viral mutation rates. J Virol<\/em>. 2010;84(19):9733-9748.<\/li>\n
  2. Hillen HS, Kokic G, Farnung L, et Structure of replicating SARS- CoV-2 polymerase. Nature<\/em>. 2020;584(7819):154-156.<\/li>\n
  3. Koyama T, Platt D, Parida L. Variant analysis of SARS-CoV-2 Bull<\/em> World<\/em> Health<\/em> Organ<\/em>. 2020;98(7):495-504.<\/li>\n<\/ol>\n
      \n
    1. Pachetti M, Marini B, Benedetti F, et Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med<\/em>. 2020;18(1):179.<\/li>\n
    2. Vilar S, Isom One Year of SARS-CoV-2: How Much Has the Virus Changed? Biology<\/em>. 2021;10(2):91. doi:10.3390\/biology10020091<\/li>\n
    3. Hadfield J, Megill C, Bell SM, et al. Nextstrain: real-time tracking of pathogen Bioinformatics<\/em>. 2018;34(23):4121-4123.<\/li>\n
    4. Volz E, Hill V, McCrone JT, et Evaluating the Effects of SARS- CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell<\/em>. 2021;184(1):64-75.e11.<\/li>\n
    5. Baric RS. Emergence of a Highly Fit SARS-CoV-2 Variant. N Engl J Med<\/em>. 2020;383(27):2684-2686.<\/li>\n
    6. Eskier D, Karak\u00fclah G, Suner A, Oktay Y. RdRp mutations are associat- ed with SARS-CoV-2 genome PeerJ<\/em>. 2020;8:e9587.<\/li>\n
    7. Begum F, Mukherjee D, Das S, et Specific mutations in SARS- CoV2 RNA dependent RNA polymerase and helicase alter protein structure, dynamics and thus function: Effect on viral RNA replication. doi:10.1101\/2020.04.26.063024<\/li>\n
    8. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike Published December 18, 2020. Accessed February 22, 2021. https:\/\/virological.org\/t\/ preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-line- age-in-the-uk-defined-by-a-novel-set-of-spike-mutations\/563<\/li>\n
    9. Tegally H, Wilkinson E, Giovanetti M, et Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS- CoV-2) lineage with multiple spike mutations in South Africa. bioRxiv<\/em>. Published online December 22, 2020. doi:10.1101\/2020.12.21.20248640<\/li>\n
    10. Genomic characterisation of an emergent SARS-CoV-2 line- age in \u00a0Manaus: \u00a0preliminary \u00a0findings. \u00a0Published \u00a0January \u00a012, \u00a02021. Accessed\u00a0\u00a0 \u00a0February\u00a0\u00a0 \u00a023,\u00a0\u00a0 \u00a02021.\u00a0\u00a0 \u00a0https:\/\/virological.org\/t\/genom- ic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-prelim- inary-findings\/586<\/li>\n
    11. Lasek-Nesselquist E, Lapierre P, Schneider E, et . The localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York State. Published online March 1, 2021. doi:10.1101\/2021.02.26.21251868<\/li>\n
    12. Kemp SA, Collier DA, Datir R, et Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation. me<\/em>dRxiv<\/em>. Published online December 29, 2020. doi:10.1101\/2020.12.05.20241927<\/li>\n
    13. WHO | SARS-CoV-2 V Published online January 22, 2021. Accessed February 22, 2021. https:\/\/www.who.i<\/a>nt\/csr\/don\/31-december-<\/a> 2020-sars-cov2-variants\/en\/<\/li>\n
    14. Volz E, Mishra S, Chand M, et Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data. doi:10.1101\/2020.12.30.20249034<\/li>\n
    15. Horby P, Huntley C, Davies N, et NERVTAG note on B. 1.1. 7 severity. New & Emerging Threats Advisory Group, Jan<\/em>. 2021;21.<\/li>\n
    16. Chand M, Others. Investigation of novel SARS-COV-2 variant: Variant of Concern 202012\/01 (PDF). Public Health England PHE<\/em>. Published online<\/li>\n
    17. Corum J, Zimmer Coronavirus Variants and Mutations. The New York Times<\/em>. https:\/\/www.nyt<\/a>imes.com\/interactive\/2021\/health\/corona-<\/a> virus-variant-tracker.html. Published March 22, 2021. Accessed April 20, 2021.<\/li>\n
    18. COVID-19: point \u00e9pid\u00e9miologique \u00e0 Mayotte du 11 f\u00e9vrier 2021.\u00a0 Accessed \u00a0February\u00a0 22,\u00a0 2021.\u00a0 https:\/\/www.santepublique- france.fr\/regions\/ocean-indien\/documents\/bulletin-regional\/2021\/cov- id-19-point-epidemiologique-a-mayotte-du-11-fevrier-2021<\/li>\n
    19. Zhou H, Dcosta BM, Samanovic MI, Mulligan MJ, Landau NR, Tada B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. bioRxiv<\/em>. Pub- lished online March 24, 2021. doi:10.1101\/2021.03.24.436620<\/li>\n
    20. Yadav PD, Sapkal GN, Abraham P, et Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. bioRxiv<\/em>. Published online April 23, 2021:2021.04.23.441101. doi:10.1101\/2021.04.23.441101<\/li>\n
    21. Tchesnokova V, Kulakesara H, Larson L, et Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants. bioRxiv<\/em>. Published online March 11, 2021. doi:10.1101\/2021.02.22.432189<\/li>\n<\/ol>\n

       <\/p>\n","protected":false},"excerpt":{"rendered":"

      *A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens Varianty v\u00edrusu SARS-CoV-2 Mut\u00e1cie s\u00fa jeden z najd\u00f4le\u017eitej\u0161\u00edch mechanizmov evol\u00facie RNA v\u00edrusov. Podobne ako in\u00e9 RNA v\u00edrusy, aj koronav\u00edrusy rutinne akumuluj\u00fa mut\u00e1cie a zmeny vo svojej gen\u00f3movej sekvencii v d\u00f4sledku nepresnosti polymer\u00e1zy(1). SARS-CoV-2 v\u0161ak obsahuje<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[1746,1727,1747,1741,1742,1743,1749,1744,1748,1745],"class_list":["post-2257","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-coronaviruses","tag-covid-19","tag-genomic-variability","tag-koronavirusy-en","tag-sars-cov-2-en","tag-sekvenovanie-en","tag-sequencing","tag-variabilita-genomu-en","tag-variants","tag-varianty-en","typ_clanku-review-article"],"acf":{"abstrakt":"

      In the past years, emerging and reappearing pathogens have become a significant challenge for global public health. A recent example of this phenomenon is zoonotic pandemics that occur after transmitting animal viruses to the human population, as is the case of the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses are the most significant encapsulated RNA viruses widely distributed among mammals, birds, and humans. They cause mainly respiratory diseases but also enteric, hepatic and neurological diseases. Currently, seven species of coronaviruses capable of infecting humans are known. Four of them cause mild clinical symptoms \u2013 229E, OC43, NL63 and HKU1, similar to a cold; and three other strains \u2013 severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV) and the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are lethal and have led to three pandemics in the 21st century. Knowledge of the SARS-CoV-2 virus sequence is a key to its characterization, and an early sharing of its genetic data allows rapid development of diagnostics. Analysis of the SARS CoV 2 genome continually shows new genome mutations. The main focus of the current research on the SARS-CoV-2 genome is to determine whether any of these mutations can significantly alter the essential viral properties that could affect the manifestation of the disease or its transmission rate.<\/p>\n

      Keywords<\/strong>: coronaviruses, SARS-Cov-2, COVID-19, genomic variability, variants, sequencing<\/p>\n","casopis":[{"ID":2233,"post_author":"7","post_date":"2021-09-19 22:32:27","post_date_gmt":"2021-09-19 20:32:27","post_content":"We\u2019re bringing you this year\u2019s 1st<\/sup> issue of newslab, the scientific journal<\/strong>\r\n\r\n \r\n

        \r\n \t
      • Genomic variability of virus Sars-CoV-2<\/li>\r\n \t
      • Contribution of immunohistochemistry to histomorphological diagnostics of COVID-19 pneumonia<\/li>\r\n \t
      • Detection of microsatellite instability in Lynch syndrome-associated tumours<\/li>\r\n \t
      • Comparison of platelet glycoprotein analysis in the wholeh blood and plasma rich in platelets<\/li>\r\n \t
      • Tspan1 expression in prostatic adenocarcinoma<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-8","to_ping":"","pinged":"","post_modified":"2021-09-19 22:36:56","post_modified_gmt":"2021-09-19 20:36:56","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/casopis\/newslab-8\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"18 - 22","upload_clanok":{"ID":2255,"id":2255,"title":"NEWSLAB 1-2021_Rusnakova","filename":"NEWSLAB-1-2021_Rusnakova.pdf","filesize":2351227,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2021\/09\/NEWSLAB-1-2021_Rusnakova.pdf","link":"https:\/\/www.newslab.sk\/en\/genomic-variability-of-sars-cov-2\/newslab-1-2021_rusnakova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab-1-2021_rusnakova-2","status":"inherit","uploaded_to":2257,"date":"2021-09-20 06:27:35","modified":"2021-09-20 06:27:35","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2257","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=2257"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2257\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=2257"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=2257"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=2257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}