„Szerkesztő:Hollófernyiges/próbalap2” változatai közötti eltérés

Ugrás a navigációhoz Ugrás a kereséshez
nincs szerkesztési összefoglaló
 
[[File:Naturalis Biodiversity Center - RMNH.MAM.33160.b dor - Rhinolophus sinicus - skin.jpeg|thumb|left|Samples taken from ''Rhinolophus sinicus'', a species of [[horseshoe bat]]s, show a 80% resemblance to SARS-CoV-2.]]
A kezdetektől fogva a denevéreket tartották a SARS-CoV-2 elsődleges természetes rezervoárjának (vagyis a vírus tünetmentesen élhet bennük, akár hosszabb ideig).<ref name="WHOChinaJoint" /><ref name="LancetBinding" /> Az eddig ismert denevérvírusok és a humán kórokozó közötti különbségek miatt azonban azt is feltételezték, hogy esetleg egy köztesgazda lehet a SARS-CoV-2 közvetlen forrása.
Bats were initially considered to be the most likely natural reservoir of SARS-CoV-2,<ref name="WHOChinaJoint" /><ref name="LancetBinding" /> which means that they harbour the virus for long periods of time with no pathogenic effects. Regarding the animal source of infection into humans, the differences between the bat coronavirus sampled at the time and SARS-CoV-2 suggested that humans were infected via an intermediate host. Arinjay Banerjee, a virologist at [[McMaster University]], notes that "the [[Severe acute respiratory syndrome coronavirus|SARS virus]] shared 99.8% of its [[genome]] with a [[civet]] coronavirus, which is why civets were considered the source."<ref name="nature feb2020" /> Although studies had suggested some likely candidates, the number and identities of intermediate hosts remains uncertain.<ref name="IJID-interm-host" /> Nearly half of the strain's genome had a phylogenetic lineage distinct from known relatives.<ref name="Rejects" />
 
[[File:Zoo Leipzig - Tou Feng.jpg|thumb|right|alt=Chinese pangolin|The [[pangolin]] coronavirus has up to 92% resemblance to SARS-CoV-2.<ref name="CurrentOrigin" />]]
Egy 2020-as filogenetikai vizsgálat azt feltételezi, hogy a tényleges vírusrezervoár valamelyik tobzoskafaj lehetett,<ref name="BMJ-Best-Practice" /> konkrét bizonyíték azonban nem áll rendelkezésre a tobzoska-ember irányú átugrásra. Az is elképzelhető, hogy az eredetileg denevérvírus megfertőzte a tobzoskákat, majd visszaugrott a denevérekre, onnan pedig az emberre. Genomja alapján a tobzoska-koronavírus távolabbi rokona a SARS-CoV-2-nek, mint a korábban említett ''Rhinolophus affinis''-féle törzs, de közelebbi, mint más denevér-koronavírusok.<ref name="CurrentOrigin" />
A [[phylogenetics]] study published in 2020 indicates that [[pangolin]]s are a reservoir host of SARS-CoV-2-like coronaviruses.<ref name="BMJ-Best-Practice" /> However, there is no direct evidence to link pangolins as an intermediate host of SARS-CoV-2 at this moment. While there is scientific consensus that bats are the ultimate source of coronaviruses, it is hypothesized that a SARS-CoV-2-like coronavirus originated in pangolins, jumped back to bats, and then jumped to humans, resulting in SARS-CoV-2. Based on whole genome sequence similarity, a pangolin coronavirus candidate strain was found to be less similar than RaTG13, but more similar than other bat coronaviruses to SARS-CoV-2.<ref name="CurrentOrigin" /> Therefore, based on [[maximum parsimony]], a specific population of bats is more likely to have directly transmitted SARS-CoV-2 to humans than a pangolin, while an evolutionary ancestor to bats was the source of general coronaviruses.<ref name="ForbesOrigin" />
 
A tobzoskák védettek Kínában, de a hagyományos kínai orvoslás felhasználja testrészeiket, ezért feketekereskedelmük jelentős.<ref name="TelegraphPangolins" /><ref name="NYT-Ban" /> Az erdőirtás, a mezőgazdaság terjedése, illegális tenyésztésük következtében a tobzoskák (és más vadállatok) olyan fajokkal kerülhetnek kapcsolatba, amelyekkel addig még nem és az emberekkel is többet érintkezhetnek, így megnő a veszélye az új zoonózisok kialakulásának.<ref>{{Cite news|last=Carrington|first=Damian|date=27 April 2020|title=Halt destruction of nature or suffer even worse pandemics, say world's top scientists|language=en-GB|work=The Guardian|url=https://www.theguardian.com/world/2020/apr/27/halt-destruction-nature-worse-pandemics-top-scientists|url-status=live|access-date=31 May 2020|issn=0261-3077|archive-url=https://web.archive.org/web/20200515015940/https://www.theguardian.com/world/2020/apr/27/halt-destruction-nature-worse-pandemics-top-scientists|archive-date=15 May 2020}}</ref>
A [[metagenomics]] study published in 2019 had previously revealed that SARS-CoV, the strain of the virus that causes SARS, was the most widely distributed coronavirus among a sample of [[Sunda pangolin]]s.<ref name="VirusesPangolins" /> On 7{{nbsp}}February 2020, [[South China Agricultural University]] in [[Guangzhou]] announced that researchers discovered a pangolin sample with a particular coronavirus – a single [[nucleic acid]] sequence of the virus was "99% similar" to that of a [[protein]]-coding [[RNA]] of SARS-CoV-2.<ref name="NaturePang" /> The authors state that "the receptor-binding domain of the [[Peplomer|S protein]] [that binds to the [[cell surface receptor]] during infection] of the newly discovered Pangolin-CoV is virtually identical to that of 2019-nCoV, with one [[amino acid]] difference."<ref name="Isolation" /> Microbiologists and geneticists in [[Texas]] have independently found evidence of [[reassortment]] in coronaviruses suggesting involvement of pangolins in the origin of SARS-CoV-2.<ref name="WongRecombination" /> The majority of the viral RNA is related to a variation of bat coronaviruses. The spike protein appears to be a notable exception, however, possibly acquired through a more recent recombination event with a pangolin coronavirus.<ref>{{Cite web|last=Timmer|first=John|date=1 June 2020|title=SARS-CoV-2 looks like a hybrid of viruses from two different species|url=https://arstechnica.com/science/2020/06/sars-cov-2-looks-like-a-hybrid-of-viruses-from-two-different-species/|access-date=6 June 2020|website=Ars Technica|language=en-us|archive-url=https://web.archive.org/web/20200605181132/https://arstechnica.com/science/2020/06/sars-cov-2-looks-like-a-hybrid-of-viruses-from-two-different-species/|archive-date=5 June 2020|url-status=live}}</ref> Structural analysis of the receptor binding domain (RBD) and human [[angiotensin-converting enzyme 2]] (ACE2) complex<ref>{{Cite journal|last1=Yan|first1=Renhong|last2=Zhang|first2=Yuanyuan|last3=Li|first3=Yaning|last4=Xia|first4=Lu|last5=Guo|first5=Yingying|last6=Zhou|first6=Qiang|date= 27 March 2020|title=Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2|journal=Science|volume=367|issue=6485|pages=1444–1448|doi=10.1126/science.abb2762|issn=1095-9203|pmc=7164635|pmid=32132184|bibcode=2020Sci...367.1444Y}}</ref> revealed key mutations on the RBD, such as F486 and N501, which form contacts with ACE2.<ref name=":0">{{Cite journal|last=Ho|first=Mitchell|s2cid=219476100|date=2020-04-30|title=Perspectives on the development of neutralizing antibodies against SARS-CoV-2|url=https://academic.oup.com/abt/article/3/2/109/5841095|journal=Antibody Therapeutics|language=en|volume=3|issue=2|pages=109–114|doi=10.1093/abt/tbaa009|pmid=32566896|pmc=7291920|access-date=14 June 2020|archive-url=https://web.archive.org/web/20200614155711/https://academic.oup.com/abt/article/3/2/109/5841095|archive-date=14 June 2020|url-status=live}}</ref> These residues are found in the pangolin coronavirus.<ref name=":0" />
 
Egyes összeesküvés-elméletek állításaival ellentétben, nem valószínű, hogy a SARS-CoV-t2-t mesterségesen hozták volna létre. Genomja nem hasonlít egyetlen korábban közölt víruséhoz sem, külső burokfehérjéje a gyakorlatban másképp viselkedik, mint amit a számítógépes szimulációs programok alapján várhatnánk, és a hatékony terjedéshez szükséges adaptációk sem jöhettek volna létre a laboratóriumokban szokásos sejtkultúrás tenyésztés során.<ref name="EA-20200317" /><ref name="Proximal" />
Pangolins are protected under Chinese law, but their [[pangolin trade|poaching and trading]] for use in [[traditional Chinese medicine]] remains common in the [[black market]].<ref name="TelegraphPangolins" /><ref name="NYT-Ban" /> [[Deforestation]], wildlife farming and trade in unsanitary conditions increases the risk of new zoonotic diseases, biodiversity experts have warned.<ref>{{Cite news|last=Carrington|first=Damian|date=27 April 2020|title=Halt destruction of nature or suffer even worse pandemics, say world's top scientists|language=en-GB|work=The Guardian|url=https://www.theguardian.com/world/2020/apr/27/halt-destruction-nature-worse-pandemics-top-scientists|url-status=live|access-date=31 May 2020|issn=0261-3077|archive-url=https://web.archive.org/web/20200515015940/https://www.theguardian.com/world/2020/apr/27/halt-destruction-nature-worse-pandemics-top-scientists|archive-date=15 May 2020}}</ref><ref>{{Cite web|title=How deforestation can lead to more infectious diseases|url=https://www.dw.com/en/how-deforestation-can-lead-to-more-infectious-diseases/a-53282244|last=Pontes|first=Nadia|date=29 April 2020|website=DW.COM|language=en-GB|url-status=live|archive-url=https://web.archive.org/web/20200505160903/https://www.dw.com/en/how-deforestation-can-lead-to-more-infectious-diseases/a-53282244|archive-date=5 May 2020|access-date=31 May 2020}}</ref><ref>{{Cite journal|last1=Cheng|first1=Vincent C. C.|last2=Lau|first2=Susanna K. P.|last3=Woo|first3=Patrick C. Y.|last4=Yuen|first4=Kwok Yung|date=October 2007|title=Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection|journal=Clinical Microbiology Reviews|volume=20|issue=4|pages=660–694|doi=10.1128/CMR.00023-07|issn=0893-8512|pmc=2176051|pmid=17934078}}</ref>
 
==Osztályozása==
It is unlikely that SARS-CoV-2 was [[Genetic engineering|genetically engineered]]. According to [[Computer simulation|computational simulations]] on [[protein folding]], the RBD of the spike protein of SARS-CoV-2 should have unremarkable binding affinity. In actuality, however, it has very efficient binding to the human ACE2 receptor. To expose the RBD for fusion, [[furin]] [[protease]]s must first cleave the S protein. Furin proteases are abundant in the respiratory tract and lung epithelial cells. Additionally, the backbone of the virus does not resemble any previously described in scientific literature used for genetic modification. The possibility that the virus could have gained the necessary [[adaptation]]s through [[cell culture]] in a laboratory setting is challenged by scientists who assert that "the generation of the predicted [[O-linked glycosylation|O-linked glycans]]... suggest[s] the involvement of an [[immune system]]."<ref name="EA-20200317" /><ref name="Proximal" />
A Vírusok Taxonómiájának Nemzetközi Bizottsága úgy foglalt állást, hogy a jelenleg érvényes szabályok szerint a COVID-19 kórokozója nem különbözik eléggé a SARS kórokozójától ahhoz, hogy önálló fajnak ismerjék el. Ennélfogva a két vírust a SARSr-CoV (súlyos akut légzőszervi szindrómához kapcsolódó koronavírus) faj két törzsének tekintik.<ref name="CoronavirusStudyGroup" />
 
A SARS-CoV-2 a Baltimore-féle taxonómiai rendszer IV. csoportjához tartozik, amelynek tagjai egyszálú, pozitív-szenz (mRNS-ként közvetlenül használható) RNS-genommal rendelkeznek. Ezen belül a Coronaviridae család és a Betacoronavirus nemzetség tagja. <ref name="Fox2020" /> Rokonai enyhább megfázásokat, de súlyos betegségeket is okozhatnak, mint a 34%-os halálozással járó közel-keleti légúti szindróma (MERS). Ez a hetedik ismert koronavírus, amely képes megfertőzni az embert (a többi a humán koronavírus 229E, NL63, OC43, HKU1 fajok, a MERS-CoV és a SARS-CoV-1).<ref name="NEJM-Novel" />
===Phylogenetics and taxonomy===
 
A 2002-es SARS-járvány vírusához hasonlóan a SARS-CoV-2 is a ''[[Sarbecovirus]]'' alnemzetség része.<ref name="NextstrainPhylogeny" /><ref name="Wong2019" /> Egyszálú RNS-genomja kb. 30 ezer bázis hosszúságú.<ref name="gisaid" /> A filogenetikai vizsgálatok szerint a világjárványért felelős kórokozó valamikor 2019 novemberében vagy decemberében jöhetett létre.<ref name="NextstrainJanuary" />
{{Infobox genome
| image = File:SARS-CoV-2 genome.svg
| caption = [[Genomic]] organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2
| taxId = 86693
| size = 29,903 bases
| year = 2020
| ucsc_assembly = wuhCor1
}}
 
==Szerkezete==
SARS-CoV-2 belongs to the broad family of viruses known as [[coronavirus]]es.<ref name="Fox2020" /> It is a [[Positive-sense single-stranded RNA virus|positive-sense single-stranded RNA]] (+ssRNA) virus, with a single linear RNA segment. Other coronaviruses are capable of causing illnesses ranging from the [[common cold]] to more severe diseases such as [[Middle East respiratory syndrome]] (MERS, fatality rate ~34%). It is the seventh known coronavirus to infect people, after [[Human coronavirus 229E|229E]], [[Human coronavirus NL63|NL63]], [[Human coronavirus OC43|OC43]], [[Human coronavirus HKU1|HKU1]], [[Middle East respiratory syndrome-related coronavirus|MERS-CoV]], and the original [[Severe acute respiratory syndrome coronavirus|SARS-CoV]].<ref name="NEJM-Novel" />
[[File:Coronavirus virion structure.svg|A SARSr-CoV virionjának szerkezete]]
 
A vírusrészecske (virion) gömb alakú, átmérője, 50–200 nanométer.<ref name="LancetCharacteristics" /> A többi koronavírushoz hasonlóan négy struktúrfehérje építi fel: az S (''spike'' a receptorhoz kötődő külső tüskét építi fel), E (''envelope''), M (''membrane'', mindkettő a lipidburokba ágyazódik) és N (''nucleocapsid'', a genomhoz kapcsolódik).<ref name="WuStructure" /> Az S protein (amelynek szerkezetét kriogenikus elektronmikroszkóppal atomi szinten felderítették) S1 alegysége kapcsolódik a sejtfelszíni receptorhoz, az S2 alegység pedig a vírus és a sejt lipidrétegeinek fúzióját katalizálja.<ref name="CEBMcoronaviruses" />
Like the SARS-related coronavirus strain implicated in the 2003 SARS outbreak, SARS-CoV-2 is a member of the subgenus ''[[Sarbecovirus]]'' ([[beta-CoV]] lineage B).<ref name="NextstrainPhylogeny" /><ref name="Wong2019" /> Its RNA sequence is approximately 30,000 [[nucleobase|base]]s in length.<ref name="gisaid" /> SARS-CoV-2 is unique among known betacoronaviruses in its incorporation of a [[polybasic cleavage site]], a characteristic known to increase [[pathogenicity]] and transmissibility in other viruses.<ref name="Proximal" /><ref name="CellWalls" /><ref name="AntiviralCleavage" />
[[File:6VSB spike protein SARS-CoV-2 monomer in homotrimer.png|thumb|A három S proteinből felépülő felszíni tüske modellje (rózsaszínnel van jelölve a receptorkötő domén)]]
 
With a sufficient number of sequenced [[genome]]s, it is possible to reconstruct a [[phylogenetic tree]] of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS-CoV-2 had been isolated from Wuhan and reported by the [[Chinese Center for Disease Control and Prevention]] (CCDC) and other institutions;<ref name="gisaid" /><ref name="VirologicalInitial" /> the number of genomes increased to 42 by 30 January 2020.<ref name="NextstrainJanuary" /> A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a [[common ancestor]]", implying that the first human infection occurred in November or December 2019.<ref name="NextstrainJanuary" /> {{As of|2020|May|7|post=,}} 4,690 SARS-CoV-2 genomes sampled on six continents were publicly available.<ref name="NexstrainApril" />
 
On 11 February 2020, the International Committee on Taxonomy of Viruses announced that according to existing rules that compute hierarchical relationships among coronaviruses on the basis of five [[conserved sequence]]s of nucleic acids, the differences between what was then called 2019-nCoV and the virus strain from the 2003 SARS outbreak were insufficient to make them separate [[viral species]]. Therefore, they identified 2019-nCoV as a [[Strain (biology)|strain]] of ''[[Severe acute respiratory syndrome-related coronavirus]]''.<ref name="CoronavirusStudyGroup" />
 
===Structural biology===
 
[[File:Coronavirus virion structure.svg|alt=Figure of a spherical SARSr-CoV virion showing locations of structural proteins forming the viral envelope and the inner nucleocapsid|thumb|right|Structure of a [[SARSr-CoV]] virion]]
 
Each SARS-CoV-2 [[virion]] is 50–200 [[nanometre]]s in diameter.<ref name="LancetCharacteristics" /> Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S ([[Peplomer|spike]]), E (envelope), M ([[membrane]]), and N ([[nucleocapsid]]) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the [[viral envelope]].<ref name="WuStructure" /> The spike protein, which has been imaged at the atomic level using [[cryogenic electron microscopy]],<ref name="SCI-20200219" /><ref name="GZM-20200220" /> is the protein responsible for allowing the virus to attach to and fuse with the [[cell membrane|membrane]] of a host cell;<ref name="WuStructure" /> specifically, its S1 subunit catalyzes attachment, the S2 subunit fusion.<ref name="CEBMcoronaviruses" />
[[File:6VSB spike protein SARS-CoV-2 monomer in homotrimer.png|thumb|upright|alt=SARS-CoV-2 spike homotrimer focusing upon one protein subunit with an ACE2 binding domain highlighted|SARS-CoV-2 spike [[homotrimer]] with one [[protein subunit]] highlighted. The ACE2 [[binding domain]] is magenta.]]
 
[[Protein structure prediction|Protein modeling]] experiments on the spike protein of the virus soon suggested that SARS-CoV-2 has sufficient affinity to the receptor [[angiotensin converting enzyme 2]] (ACE2) on human cells to use them as a mechanism of [[Viral entry|cell entry]].<ref name="SCLSModeling" /> By 22 January 2020, a group in China working with the full virus genome and a group in the United States using [[reverse genetics]] methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS-CoV-2.<ref name="NatureZhou" /><ref name="Letko22Jan2020" /><ref name="NatMicLetko" /><ref name="ElSahly" /> Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.<ref name="SCI-20200219" /><ref name="NIH-Structure" /> SARS-CoV-2 may also use [[basigin]] to assist in cell entry.<ref name="CD147" />

Navigációs menü