SARS-CoV-2: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Skazmi moved page Novel Coronavirus to 2019-nCoV over redirect)
 
(57 intermediate revisions by 5 users not shown)
Line 1: Line 1:
The '''novel coronavirus''' ('''2019-nCoV'''), also known as the '''Wuhan coronavirus''',<ref name="Fox2020" /> and named '''Covid-19''' by [[World Health Organization|WHO]]''',''' is a contagious virus that causes respiratory infection and has shown evidence of human-to-human transmission, first identified by authorities in [[Wuhan]], [[Hubei]], [[China]], as the cause of the ongoing [[2019–20 Wuhan coronavirus outbreak|2019–20 Wuhan coronavirus outbreak]]. [[Genomic sequencing]] has shown that it is a [[Positive-sense single-stranded RNA virus|positive-sense, single-stranded RNA]] [[coronavirus]].
__NOTOC__
{{COVID-19}}


Due to reports that the initial cases had epidemiological links to a large seafood and animal market, the virus is thought to have a [[zoonotic]] origin, though this has not been confirmed. Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to [[SARS-CoV]] (79.5%) and bat coronaviruses (96%),<ref name=":2" /> with a likely origin in bats being theorized.<ref name=":3" /><ref name=":4" />
'''Editor-In-Chief:''' [[User:C Michael Gibson|C. Michael Gibson, M.S., M.D.]] [[Mailto:charlesmichaelgibson@gmail.com|[1]]]; '''Associate Editor(s)-in-Chief:'''  {{Syed rizvi}}
==Overview==
The  [[COVID-19|Coronavirus disease-2019]] ([[COVID-19]]), is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 forms a distinct lineage with bat [[SARS]]-like [[Coronavirus|coronaviruses]] . The virus is closely related (96.3%) to bat coronavirus RaTG13, based on [[phylogenetic]] analysis, that belong to the order [[Nidovirales]], family [[Coronaviridae]], genus Betacoronavirus, and subgenus Sarbecovirus . Coronaviruses are [[Enveloped virus|enveloped]], single-stranded [[RNA virus|RNA viruses]] that can infect a wide range of hosts including avian, wild, domestic mammalian species, and humans. [[Coronavirus|Coronaviruses]] are well known for their ability to [[Mutation|mutate]] rapidly, alter [[tissue tropism]], cross the species barrier, and adapt to different [[Epidemiology|epidemiological]] situations. Six human [[coronaviruses]] have been reported since the 1960s; OC43, 229E, NL63, HKU1, severe acute respiratory syndrome coronavirus ([[SARS-CoV]]) and [[Middle East respiratory syndrome coronavirus infection|Middle East respiratory syndrome coronavirus]] ([[MERS-CoV]]). First case of [[COVID-19]] was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. On March 11, 2020 the [[COVID-19|Novel Coronavirus Disease]], [[COVID-19]], was declared a [[pandemic]] by the World Health Organization
<br />
==Taxonomy ==


==Epidemiology==
*
{{Main article|2019–20 Wuhan coronavirus outbreak}}
*
*
*
*
*
*
*
*
*
*


The first known human infection occurred in early December 2019. [[Molecular clock]] approaches suggest a similar, or slightly earlier, date of origin.
*SARS-CoV-2 belong to the order [[Nidovirales|nidovirale]], family [[coronaviridae]].<ref name="ZhouYang2020">{{cite journal|last1=Zhou|first1=Peng|last2=Yang|first2=Xing-Lou|last3=Wang|first3=Xian-Guang|last4=Hu|first4=Ben|last5=Zhang|first5=Lei|last6=Zhang|first6=Wei|last7=Si|first7=Hao-Rui|last8=Zhu|first8=Yan|last9=Li|first9=Bei|last10=Huang|first10=Chao-Lin|last11=Chen|first11=Hui-Dong|last12=Chen|first12=Jing|last13=Luo|first13=Yun|last14=Guo|first14=Hua|last15=Jiang|first15=Ren-Di|last16=Liu|first16=Mei-Qin|last17=Chen|first17=Ying|last18=Shen|first18=Xu-Rui|last19=Wang|first19=Xi|last20=Zheng|first20=Xiao-Shuang|last21=Zhao|first21=Kai|last22=Chen|first22=Quan-Jiao|last23=Deng|first23=Fei|last24=Liu|first24=Lin-Lin|last25=Yan|first25=Bing|last26=Zhan|first26=Fa-Xian|last27=Wang|first27=Yan-Yi|last28=Xiao|first28=Geng-Fu|last29=Shi|first29=Zheng-Li|title=A pneumonia outbreak associated with a new coronavirus of probable bat origin|journal=Nature|volume=579|issue=7798|year=2020|pages=270–273|issn=0028-0836|doi=10.1038/s41586-020-2012-7}}</ref>
*[[Coronaviridae]] is classified into two subfamilies.
**Torovirinae
**Coronavirinae
*Coronavirinae is further classified on the basis of [[Phylogenetics|phylogenetic]] analysis and [[genome]] structure into four genera:
**Alpha coronavirus (αCoV).
**Beta coronavirus (βCoV).
**Gamma coronavirus (γCoV).
**Delta coronavirus (δCoV), which contain 17, 12, 2, and 7 unique species, respectively (ICTV 2018).
*__NOTOC__CoV-2 falls under beta coronavirus.


An outbreak of 2019-nCoV was first detected in [[Wuhan]], China, in mid-December 2019. The virus subsequently spread to other provinces of Mainland China and other countries, including Thailand, Japan, Taiwan, South Korea, Australia, France, and the United States.
{| border="1" cellpadding="5" cellspacing="0" align="center" |class="wikitable"
|+
!style="background:#efefef;" |Stuructural Protein
!style="background:#efefef;" |Function of protein
|-
|Spike (S) Protein
|Critical for binding to host cell receptor (ACE-2 receptor) and facilitate entry to host cell.<ref name="MathewsonBishop2008">{{cite journal|last1=Mathewson|first1=Alison C.|last2=Bishop|first2=Alexandra|last3=Yao|first3=Yongxiu|last4=Kemp|first4=Fred|last5=Ren|first5=Junyuan|last6=Chen|first6=Hongying|last7=Xu|first7=Xiaodong|last8=Berkhout|first8=Ben|last9=van der Hoek|first9=Lia|last10=Jones|first10=Ian M.|title=Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2|journal=
Journal of General Virology
|volume=89|issue=11|year=2008|pages=2741–2745|issn=0022-1317|doi=10.1099/vir.0.2008/003962-0}}</ref><ref name="pmid14647384">{{cite journal |vauthors=Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M |title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus |journal=Nature |volume=426 |issue=6965 |pages=450–4 |date=November 2003 |pmid=14647384 |pmc=7095016 |doi=10.1038/nature02145 |url=}}</ref>
|-
|Envelope (E) Protein
|[[Viral envelope|Envelope (E) protein]] is a small, integral membrane protein involved in several aspects of the [[virus]]’ life cycle, such as assembly,  
budding, envelope formation, and [[pathogenesis]].<ref name="SchoemanFielding20194">{{cite journal|last1=Schoeman|first1=Dewald|last2=Fielding|first2=Burtram C.|title=Coronavirus envelope protein: current knowledge|journal=Virology Journal|volume=16|issue=1|year=2019|issn=1743-422X|doi=10.1186/s12985-019-1182-0}}</ref>
|-
|Membrane (M) Protein
|Membrane (M) protein is a component of the [[viral envelope]] that plays a central role in [[virus]]
[[morphogenesis]] and assembly via its interactions with other viral proteins<ref name="FehrPerlman2015">{{cite journal|last1=Fehr|first1=Anthony R.|last2=Perlman|first2=Stanley|title=Coronaviruses: An Overview of Their Replication and Pathogenesis|volume=1282|year=2015|pages=1–23|issn=1064-3745|doi=10.1007/978-1-4939-2438-7_1}}</ref>
|-
|Nucleocapsid (N) Protein
|[[Nucleocapsid]] (N) protein is to package the viral RNA genome within the [[viral envelope]] into a [[ribonucleoprotein]] (RNP)
complex called the [[capsid]].<ref name="pmid25105276">{{cite journal |vauthors=McBride R, van Zyl M, Fielding BC |title=The coronavirus nucleocapsid is a multifunctional protein |journal=Viruses |volume=6 |issue=8 |pages=2991–3018 |date=August 2014 |pmid=25105276 |pmc=4147684 |doi=10.3390/v6082991 |url=}}</ref>
|}<br />
====Structural Proteins====


As of 29 January 2020 (04:00 UTC), there were 6,057 confirmed cases of infection, of which 5,970 were within mainland China. Cases outside China, to date, were people who have either travelled from Wuhan, or were in direct contact with someone who travelled from the area. The number of deaths was 132 as of 29 January 2020 (04:00 UTC).<ref name="GI2020Update" /> Human-to-human spread was first confirmed in [[Guangdong]], China, on 20 January 2020.
*'''Spike (S) Protein <ref name="MathewsonBishop2008" /><ref name="pmid14647384" />'''
** Cell entry of [[Coronavirus|coronaviruses]] depends on binding of the viral spike (S) proteins to cellular [[receptors]] and on S protein priming by host cell [[Protease|proteases]].
**Early studies indicate that SARS-CoV-2 uses the [[SARS-CoV]] receptor [[angiotensin-converting enzyme 2]] [[Angiotensin-converting enzyme 2|(ACE2]]) for entry and [[Transmembrane protein|transmembrane protease serine 2]] (TMPRSS2) for S protein priming.<ref name="MathewsonBishop20082">{{cite journal|last1=Mathewson|first1=Alison C.|last2=Bishop|first2=Alexandra|last3=Yao|first3=Yongxiu|last4=Kemp|first4=Fred|last5=Ren|first5=Junyuan|last6=Chen|first6=Hongying|last7=Xu|first7=Xiaodong|last8=Berkhout|first8=Ben|last9=van der Hoek|first9=Lia|last10=Jones|first10=Ian M.|title=Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2|journal=
Journal of General Virology
|volume=89|issue=11|year=2008|pages=2741–2745|issn=0022-1317|doi=10.1099/vir.0.2008/003962-0}}</ref><ref name="ZhouYang20203">{{cite journal|last1=Zhou|first1=Peng|last2=Yang|first2=Xing-Lou|last3=Wang|first3=Xian-Guang|last4=Hu|first4=Ben|last5=Zhang|first5=Lei|last6=Zhang|first6=Wei|last7=Si|first7=Hao-Rui|last8=Zhu|first8=Yan|last9=Li|first9=Bei|last10=Huang|first10=Chao-Lin|last11=Chen|first11=Hui-Dong|last12=Chen|first12=Jing|last13=Luo|first13=Yun|last14=Guo|first14=Hua|last15=Jiang|first15=Ren-Di|last16=Liu|first16=Mei-Qin|last17=Chen|first17=Ying|last18=Shen|first18=Xu-Rui|last19=Wang|first19=Xi|last20=Zheng|first20=Xiao-Shuang|last21=Zhao|first21=Kai|last22=Chen|first22=Quan-Jiao|last23=Deng|first23=Fei|last24=Liu|first24=Lin-Lin|last25=Yan|first25=Bing|last26=Zhan|first26=Fa-Xian|last27=Wang|first27=Yan-Yi|last28=Xiao|first28=Geng-Fu|last29=Shi|first29=Zheng-Li|title=A pneumonia outbreak associated with a new coronavirus of probable bat origin|journal=Nature|volume=579|issue=7798|year=2020|pages=270–273|issn=0028-0836|doi=10.1038/s41586-020-2012-7}}</ref>
**The spike (S) [[glycoprotein]] is a type I [[Transmembrane protein|transmembrane]] glycoprotein that plays an important role in mediating [[viral infection]].
**The S proteins consist of two subunits, S1 and S2.
**The S1 subunit binds the cellular receptor through its receptor-binding domain (RBD), followed by conformational changes in the S2 subunit, which allows the fusion peptide to insert into the host target cell membrane.<ref name="NievaCarrasco2015">{{cite journal|last1=Nieva|first1=José|last2=Carrasco|first2=Luis|title=Viroporins: Structures and functions beyond cell membrane permeabilization|journal=Viruses|volume=7|issue=10|year=2015|pages=5169–5171|issn=1999-4915|doi=10.3390/v7102866}}</ref>


==Treatment==
*'''Envelope (E) Protein<ref name="SchoemanFielding20194" />'''
No specific treatment is currently available, so treatment is focused on alleviation of symptoms,<ref name="thomreut_antivirals" /> which include [[fever]], [[fatigue]], [[dry cough]], and [[shortness of breath]], or [[pneumonia]] and [[kidney failure]] in severe cases. The [[Chinese Center for Disease Control and Prevention]] (CCDC) is testing existing pneumonia treatments for efficacy in treating coronavirus-related pneumonia.
**The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the [[virus]]’ life cycle, such as assembly, budding, envelope formation, and pathogenesis.<ref name="SchoemanFielding20192">{{cite journal|last1=Schoeman|first1=Dewald|last2=Fielding|first2=Burtram C.|title=Coronavirus envelope protein: current knowledge|journal=Virology Journal|volume=16|issue=1|year=2019|issn=1743-422X|doi=10.1186/s12985-019-1182-0}}</ref>
**Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins.<ref name="SchoemanFielding20193">{{cite journal|last1=Schoeman|first1=Dewald|last2=Fielding|first2=Burtram C.|title=Coronavirus envelope protein: current knowledge|journal=Virology Journal|volume=16|issue=1|year=2019|issn=1743-422X|doi=10.1186/s12985-019-1182-0}}</ref>
**Recombinant CoVs lacking E exhibit significantly reduced viral titres, crippled viral maturation, or yield propagation incompetent progeny, demonstrating the importance of E in virus production and maturation.<ref name="SchoemanFielding2019">{{cite journal|last1=Schoeman|first1=Dewald|last2=Fielding|first2=Burtram C.|title=Coronavirus envelope protein: current knowledge|journal=Virology Journal|volume=16|issue=1|year=2019|issn=1743-422X|doi=10.1186/s12985-019-1182-0}}</ref>


Existing [[antiviral drug|anti-virals]] are being studied, including [[Protease inhibitor (pharmacology)|protease inhibitors]] like [[indinavir]], [[saquinavir]], [[remdesivir]], [[lopinavir/ritonavir]] and [[interferon beta]]. The effectiveness of previously identified [[monoclonal antibodies]] (mAbs) is also under investigation.
<br />[[File:SARS-Cov-2 protien.jpg|thumb|Structure Protein of Coronavirus <ref name="SeahSu2020">{{cite journal|last1=Seah|first1=Ivan|last2=Su|first2=Xinyi|last3=Lingam|first3=Gopal|title=Revisiting the dangers of the coronavirus in the ophthalmology practice|journal=Eye|volume=34|issue=7|year=2020|pages=1155–1157|issn=0950-222X|doi=10.1038/s41433-020-0790-7}}</ref>|center]]<br />


==Virology==
*'''Membrane (M) Protein <ref name="FehrPerlman2015" />'''
===Infection===
**The CoV membrane (M) protein is a component of the [[viral envelope]] that plays a central role in [[virus]] [[morphogenesis]] and assembly via its interactions with other [[viral]] [[proteins]].
Human-to-human transmission of the virus has been confirmed.<ref name="auto" /> Reports have emerged that the virus is infectious even during the [[incubation period]], although as of 27 January 2020 officials at the [[Centers for Disease Control and Prevention]] (CDC) in the United States stated they "don't have any evidence of patients being infectious prior to symptom onset."
**M is located among the S proteins in the [[Viral envelope|virus envelope]] along with small amounts of E and is the primary driver of the [[Budding|virus budding process]].
**During assembly of the authentic virion M interacts with itself, with the [[nucleocapsid]] protein N, with E and with the S protein.
**The M protein has [[dominant]] cellular [[immunogenicity]] and elicits a strong [[Antibody responses|humoral response]] which suggests it could serve as a potential target in [[vaccine]] design.<ref name="SiuTeoh2008">{{cite journal|last1=Siu|first1=Y. L.|last2=Teoh|first2=K. T.|last3=Lo|first3=J.|last4=Chan|first4=C. M.|last5=Kien|first5=F.|last6=Escriou|first6=N.|last7=Tsao|first7=S. W.|last8=Nicholls|first8=J. M.|last9=Altmeyer|first9=R.|last10=Peiris|first10=J. S. M.|last11=Bruzzone|first11=R.|last12=Nal|first12=B.|title=The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles |journal=Journal of Virology|volume=82|issue=22|year=2008|pages=11318–11330|issn=0022-538X|doi=10.1128/JVI.01052-08}}</ref> <ref name="pmid6325194">{{cite journal |vauthors=Tooze J, Tooze S, Warren G |title=Replication of coronavirus MHV-A59 in sac- cells: determination of the first site of budding of progeny virions |journal=Eur. J. Cell Biol. |volume=33 |issue=2 |pages=281–93 |date=March 1984 |pmid=6325194 |doi= |url=}}</ref>


Research groups have estimated the [[basic reproduction number]] (<math>R_0</math>, pronounced ''R-nought'') of the virus to be between 1.4 and 5, with most estimates below 3.8. This means that, when unchecked, the virus typically results in 1.4 to 3.8 new cases per established infection. It has been established that the virus is able to transmit along a chain of at least four people.
*'''Nucleocapsid (N) Protein'''<ref name="pmid251052762">{{cite journal |vauthors=McBride R, van Zyl M, Fielding BC |title=The coronavirus nucleocapsid is a multifunctional protein |journal=Viruses |volume=6 |issue=8 |pages=2991–3018 |date=August 2014 |pmid=25105276 |pmc=4147684 |doi=10.3390/v6082991 |url=}}</ref>
** The primary function of the nucleocapsid (N) protein is to package the viral RNA [[genome]] within the viral envelope into a ribonucleoprotein (RNP) complex called the capsid.
**[[Ribonucleoprotein|Ribonucleocapsid]] packaging is a fundamental part of viral self-assembly and replication.
**Additionally, the N-protein of the SARS-CoV-2 affects host cell responses and may serve regulatory roles during its viral life cycle.<br />


===Reservoir===
=== CORONA VIRUS LIFE CYCLE: ===
Animals sold for food are suspected to be the reservoir or the intermediary because many of the first identified infected individuals were workers at the [[Huanan Seafood Market]]. Consequently, they were exposed to greater contact with animals.<ref name="Hui14Jan2020" /> A market selling live animals for food was also blamed in the [[Severe acute respiratory syndrome|SARS epidemic]] in 2003; such markets are considered to be incubators for novel pathogens. The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.
[[File:Coronavirus-Cycle-Simplified-2048x1463.jpg|thumb|529x529px|[[CORONA]]<ref>{{Cite web|url=https://doi.org/10.3390/pathogens9050331|title=The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms|last=|first=Lo’ai Alanagreh .Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa 13133, Jordan|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> VIRUS LIFECYCLE]]


With a sufficient number of [[DNA sequencing|sequenced]] genomes, it is possible to reconstruct a [[phylogenetic tree]] of the mutation history of a family of viruses. During 17 years of research on the origin of the [[SARS]] 2003 epidemic, many [[Bat SARS-like coronavirus WIV1|SARS-like bat coronaviruses]] were isolated and sequenced, most of them originating from the ''[[Rhinolophus]]'' genus of bats. 2019-nCoV has been found to fall into this category of SARS-related coronaviruses. Two genome sequences from ''[[Rhinolophus sinicus]]'' published in 2015 and 2017 show a resemblance of 80% to 2019-nCoV. A third unpublished virus genome from ''[[Intermediate horseshoe bat|Rhinolophus affinis]]'', "RaTG13", is said to have a 96% resemblance to 2019-nCoV. For comparison, this amount of variation among viruses is similar to the amount of mutation observed over ten years in the H3N2 human flu virus strain.
===<small>Attachment and Entry</small>:===


===Phylogenetics and taxonomy===
*The attachment of the virion to the host cell is associated with the  interactions between the S protein and its receptor.
{{Infobox genome
*The sites of receptor binding domains (RBD) within the S1 region of a coronavirus (SARS-CoV-2)  S protein is at the C Terminus.<ref name="pmid7520090">{{cite journal |vauthors=Kubo H, Yamada YK, Taguchi F |title=Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein |journal=J. Virol. |volume=68 |issue=9 |pages=5403–10 |date=September 1994 |pmid=7520090 |pmc=236940 |doi= |url=}}</ref>
| image      = File:2019-nCoV genome.svg
*SARS-CoV use [[angiotensin-converting enzyme 2]] (ACE2) as their receptor<ref name="ZhouYang20204">{{cite journal|last1=Zhou|first1=Peng|last2=Yang|first2=Xing-Lou|last3=Wang|first3=Xian-Guang|last4=Hu|first4=Ben|last5=Zhang|first5=Lei|last6=Zhang|first6=Wei|last7=Si|first7=Hao-Rui|last8=Zhu|first8=Yan|last9=Li|first9=Bei|last10=Huang|first10=Chao-Lin|last11=Chen|first11=Hui-Dong|last12=Chen|first12=Jing|last13=Luo|first13=Yun|last14=Guo|first14=Hua|last15=Jiang|first15=Ren-Di|last16=Liu|first16=Mei-Qin|last17=Chen|first17=Ying|last18=Shen|first18=Xu-Rui|last19=Wang|first19=Xi|last20=Zheng|first20=Xiao-Shuang|last21=Zhao|first21=Kai|last22=Chen|first22=Quan-Jiao|last23=Deng|first23=Fei|last24=Liu|first24=Lin-Lin|last25=Yan|first25=Bing|last26=Zhan|first26=Fa-Xian|last27=Wang|first27=Yan-Yi|last28=Xiao|first28=Geng-Fu|last29=Shi|first29=Zheng-Li|title=A pneumonia outbreak associated with a new coronavirus of probable bat origin|journal=Nature|volume=579|issue=7798|year=2020|pages=270–273|issn=0028-0836|doi=10.1038/s41586-020-2012-7}}</ref>
| caption    = [[Genome]] organisation (click to enlarge)
*After binding to the receptor, the virus next step is to gain access to the host cell cytosol.
| type        = nucleotide
*This is generally done by [[cathepsin]],TMPRRS2 or some other [[protease]]. This is followed by fusion of the viral and [[Cell membranes|cellular membranes]].
| taxId      = MN908947
*S protein cleavage occurs at two sites within the S2 portion of the [[protein]], with the first cleavage important for separating the RBD (Receptor binding domain) and fusion domains of the S protein <ref name="pmid19321428">{{cite journal |vauthors=Belouzard S, Chu VC, Whittaker GR |title=Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=106 |issue=14 |pages=5871–6 |date=April 2009 |pmid=19321428 |pmc=2660061 |doi=10.1073/pnas.0809524106 |url=}}</ref> and the second for exposing the fusion peptide (cleavage at S2′).
| size        = 29,903 bases
*Fusion occurs within acidified [[endosomes]].
| year       = 2020
* Cleavage at S2′ exposes a fusion [[peptide]] that inserts into the membrane, which is followed by joining of two heptad repeats in S2 forming an antiparallel six-helix bundle<ref name="pmid2885899">{{cite journal |vauthors=Knuhtsen S, Holst JJ, Schwartz TW, Jensen SL, Nielsen OV |title=The effect of gastrin-releasing peptide on the endocrine pancreas |journal=Regul. Pept. |volume=17 |issue=5 |pages=269–76 |date=May 1987 |pmid=2885899 |doi=10.1016/0167-0115(87)90284-9 |url=}}</ref>.The formation of this bundle allows for the mixing of viral and cellular membranes, resulting in fusion and ultimately release of the viral genome into the cytoplasm.
}}
2019-nCoV belongs to the broad family of viruses known as [[coronavirus]]es. Other coronaviruses are capable of causing illnesses ranging from the [[common cold]] to more severe diseases such as the [[Middle East respiratory syndrome]] (MERS) and [[severe acute respiratory syndrome]] (SARS). 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 [[Severe acute respiratory syndrome-related coronavirus|SARS-CoV]].


Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus ''[[Sarbecovirus]]'' (Beta-CoV lineage B).<ref name="Hui14Jan2020" /> Its [[RNA]] sequence is approximately 30 [[Base pair#Length measurements|kb]] in length.<ref name=":1" />
===='''RNA Replicase Protein Expression:'''====


By 12 January, five genomes of the novel coronavirus had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention and other institutions;<ref name=":1" /> the number of genomes increased to 28 by 26 January. Except for the earliest GenBank genome, the genomes are under an embargo at [[GISAID]]. A phylogenic analysis for the samples is available through Nextstrain.
*The next step in the coronavirus lifecycle is [[Translation (genetics)|translation]] and assembly of the viral replicase complexes  from the [[virion]] genomic RNA.


=== Structural biology ===
==== Replication and Transcription:====
[[File:Coronavirus 2019-nCoV.3.png|thumb|right|Innophore [[Phyre2]] [[ribbon diagram]] of the 2019-nCoV M(pro) [[Protease#Viruses|protease]], a prospective target for [[Antiviral_drug#Protease_inhibitors|antiviral drug]]s<ref name="inno-dock" />]]
The publications of the genome led to several [[Protein_structure_prediction|protein modeling]] experiments on the receptor binding protein (RBD) of the nCoV spike (S) protein suggesting that the S protein retained sufficient affinity to the [[Angiotensin converting enzyme 2]] (ACE2) receptor to use it as a mechanism of cell entry. On 22 January, a group in China working with the full virus and a group in the U.S. working with reverse genetics independently and experimentally demonstrated ACE2 as the receptor for 2019-nCoV.


To look for potential [[protease inhibitor (pharmacology)|protease inhibitors]], the viral [[3C-like protease]] M(pro) from the Orf1a polyprotein was also modeled for drug docking experiments. Innophore has produced two computational models based on SARS protease, and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.<!-- Authors are Rao ZH, Yang HT; check PDB daily -->
*The [[Translation (genetics)|translation]] and assembly of the viral replicase complexes is followed by viral [[RNA synthesis|RNA synthesi]]<nowiki/>s.
*Viral RNA synthesis produces both genomic and sub-genomic RNAs.
*Sub-genomic RNAs serve as [[mRNA]]<nowiki/>s for the structural and accessory [[genes]] which reside downstream of the replicase polyproteins. All [[Positive-sense RNA|positive-sense]] sub-genomic RNAs are 3′ co-terminal with the full-length viral genome and thus form a set of nested RNAs, a distinctive property of the order ''[[Nidovirales]]''. Both genomic and sub-genomic RNAs are produced through [[negative-sense]] intermediates. These negative-strand intermediates are only about 1 % as abundant as their [[Positive-sense RNA|positive-sense]] counterparts and contain both poly-uridylate and anti-leader sequences.<ref name="pmid1985203">{{cite journal |vauthors=Sethna PB, Hofmann MA, Brian DA |title=Minus-strand copies of replicating coronavirus mRNAs contain antileaders |journal=J. Virol. |volume=65 |issue=1 |pages=320–5 |date=January 1991 |pmid=1985203 |pmc=240520 |doi= |url=}}</ref>


== Vaccine research ==
==== Assembly and Release: ====
In January 2020, several organizations and institutions began work on creating [[vaccine]]s for 2019 n-CoV based on the published genome.<ref name="ThomReut_NIH_Moderna_3months" /><ref name="CBC_Saskatch_6_8_weeks_nonhuman" />


In China, the Chinese Center for Disease Control and Prevention is developing a vaccine against the novel coronavirus.<ref name="auto1" /> The team of [[Yuen Kwok-yung]] at the [[University of Hong Kong]], which previously participated in work on the SARS coronavirus during its 2003 outbreak, has also announced that a vaccine is under development there but has yet to proceed to animal testing.
* After replication and transcription, the structural proteins of virus ( S,M,E) are translated and then inserted into [[endoplasmic reticulum]]. From [[endoplasmic reticulum]] they are taken to endoplasmic reticulum-Golgi intermediate compartment.<ref name="pmid8294506">{{cite journal |vauthors=Krijnse-Locker J, Ericsson M, Rottier PJ, Griffiths G |title=Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step |journal=J. Cell Biol. |volume=124 |issue=1-2 |pages=55–70 |date=January 1994 |pmid=8294506 |pmc=2119890 |doi=10.1083/jcb.124.1.55 |url=}}</ref>
* Here the N protein encapsidate the viral [[genome]], and  bud into membranes of the endoplasmic reticulum-Golgi intermediate compartment containing viral structural proteins, thus forming mature virion.<ref name="pmid16139595">{{cite journal |vauthors=de Haan CA, Rottier PJ |title=Molecular interactions in the assembly of coronaviruses |journal=Adv. Virus Res. |volume=64 |issue= |pages=165–230 |date=2005 |pmid=16139595 |pmc=7112327 |doi=10.1016/S0065-3527(05)64006-7 |url=}}</ref>
*Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.<br />
==Tropism==


Elsewhere, three vaccine projects are being supported by the [[Coalition for Epidemic Preparedness Innovations]] (CEPI), including one project by the [[biotechnology]] company [[Moderna]] and another by the [[University of Queensland]].<ref name="Guardian_CEPI_16weeks" /> The United States [[National Institutes of Health]] (NIH) is cooperating with Moderna to create an RNA vaccine matching a spike of the coronavirus surface, and is hoping to start production by May 2020.<ref name="ThomReut_NIH_Moderna_3months" /> In Australia, the University of Queensland is investigating the potential of a molecular clamp vaccine that would genetically modify viral proteins to make them mimic the coronavirus and stimulate an immune reaction.<ref name="Guardian_CEPI_16weeks" />
* Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects cells in the [[respiratory tract]], which is [[lung]] [[Alveolus|alveolar epithelial cell]] .<ref name="pmid32074444">{{cite journal |vauthors=Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J |title=SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients |journal=N. Engl. J. Med. |volume=382 |issue=12 |pages=1177–1179 |date=March 2020 |pmid=32074444 |pmc=7121626 |doi=10.1056/NEJMc2001737 |url=}}</ref><ref name="pmid32226285">{{cite journal |vauthors=Zheng J |title=SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat |journal=Int. J. Biol. Sci. |volume=16 |issue=10 |pages=1678–1685 |date=2020 |pmid=32226285 |pmc=7098030 |doi=10.7150/ijbs.45053 |url=}}</ref>
* SARS-CoV-2 can be detected in multiple organs, including the [[lungs]], [[heart]], [[liver]], [[brain]], [[pharynx]] and [[Kidney|kidneys]].<ref name="pmid32402155">{{cite journal |vauthors=Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB |title=Multiorgan and Renal Tropism of SARS-CoV-2 |journal=N. Engl. J. Med. |volume= |issue= |pages= |date=May 2020 |pmid=32402155 |pmc=7240771 |doi=10.1056/NEJMc2011400 |url=}}</ref>
* Highest levels of SARS-CoV-2 copies per cell were presumed to be detected in the [[respiratory tract]], and lower levels were detected the [[kidneys]], [[liver]], [[heart]], [[brain]], and [[blood]].
**These findings indicate a broad organotropism of SARS-CoV-2.<ref name="pmid324021552">{{cite journal |vauthors=Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB |title=Multiorgan and Renal Tropism of SARS-CoV-2 |journal=N. Engl. J. Med. |volume= |issue= |pages= |date=May 2020 |pmid=32402155 |pmc=7240771 |doi=10.1056/NEJMc2011400 |url=}}</ref>


In an independent project, the [[Public Health Agency of Canada]] has granted permission to the [[Vaccine and Infectious Disease Organization|International Vaccine Centre]] (VIDO-InterVac) at the [[University of Saskatchewan]] to begin work on a vaccine. VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.<ref name="CBC_Saskatch_6_8_weeks_nonhuman" />
<br />
==Natural Reservoir==
 
* Current evidences suggest that the evolutional origin of SARS-CoV-2 is from bat virus an intermediate host between bats and human might exist.<ref name="pmid32007145">{{cite journal |vauthors=Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W |title=Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding |journal=Lancet |volume=395 |issue=10224 |pages=565–574 |date=February 2020 |pmid=32007145 |pmc=7159086 |doi=10.1016/S0140-6736(20)30251-8 |url=}}</ref><ref name="WuZhao2020">{{cite journal|last1=Wu|first1=Fan|last2=Zhao|first2=Su|last3=Yu|first3=Bin|last4=Chen|first4=Yan-Mei|last5=Wang|first5=Wen|last6=Song|first6=Zhi-Gang|last7=Hu|first7=Yi|last8=Tao|first8=Zhao-Wu|last9=Tian|first9=Jun-Hua|last10=Pei|first10=Yuan-Yuan|last11=Yuan|first11=Ming-Li|last12=Zhang|first12=Yu-Ling|last13=Dai|first13=Fa-Hui|last14=Liu|first14=Yi|last15=Wang|first15=Qi-Min|last16=Zheng|first16=Jiao-Jiao|last17=Xu|first17=Lin|last18=Holmes|first18=Edward C.|last19=Zhang|first19=Yong-Zhen|title=A new coronavirus associated with human respiratory disease in China|journal=Nature|volume=579|issue=7798|year=2020|pages=265–269|issn=0028-0836|doi=10.1038/s41586-020-2008-3}}</ref>
* Potential intermediate host for SARS-CoV-2 can be [[pangolin]].
*Novel coronaviruses representing two sub-lineages related to SARS-CoV-2 were found in the samples of malytan [[pangolin]]<nowiki/>s.<ref name="LamShum2020">{{cite journal|last1=Lam|first1=Tommy Tsan-Yuk|last2=Shum|first2=Marcus Ho-Hin|last3=Zhu|first3=Hua-Chen|last4=Tong|first4=Yi-Gang|last5=Ni|first5=Xue-Bing|last6=Liao|first6=Yun-Shi|last7=Wei|first7=Wei|last8=Cheung|first8=William Yiu-Man|last9=Li|first9=Wen-Juan|last10=Li|first10=Lian-Feng|last11=Leung|first11=Gabriel M|last12=Holmes|first12=Edward C.|last13=Hu|first13=Yan-Ling|last14=Guan|first14=Yi|year=2020|doi=10.1101/2020.02.13.945485}}</ref>
*The similarity of SARS-CoV-2 to these identified [[Coronavirus|coronaviruses]] from [[Pangolin|pangolins]] is approximately 85.5% to 92.4% in genomes, lower than that to the bat coronavirus RaTG13 (96.2%) 14,62.
*However, the receptor-binding domain of S protein from one sub-lineage of the pangolin coronaviruses shows 97.4% similarity in amino acid sequences to that of SARS-CoV-2, even higher than that to RaTG13 (89.2%).<ref name="LamShum20202">{{cite journal|last1=Lam|first1=Tommy Tsan-Yuk|last2=Shum|first2=Marcus Ho-Hin|last3=Zhu|first3=Hua-Chen|last4=Tong|first4=Yi-Gang|last5=Ni|first5=Xue-Bing|last6=Liao|first6=Yun-Shi|last7=Wei|first7=Wei|last8=Cheung|first8=William Yiu-Man|last9=Li|first9=Wen-Juan|last10=Li|first10=Lian-Feng|last11=Leung|first11=Gabriel M|last12=Holmes|first12=Edward C.|last13=Hu|first13=Yan-Ling|last14=Guan|first14=Yi|year=2020|doi=10.1101/2020.02.13.945485}}</ref>
*


==References==
==References==
{{reflist|2}}<br />
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 18:17, 20 July 2020

COVID-19 Microchapters

Home

Long COVID

Frequently Asked Outpatient Questions

Frequently Asked Inpatient Questions

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating COVID-19 from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary Prevention

Vaccines

Secondary Prevention

Future or Investigational Therapies

Ongoing Clinical Trials

Case Studies

Case #1

SARS-CoV-2 On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of SARS-CoV-2

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on SARS-CoV-2

CDC on SARS-CoV-2

SARS-CoV-2 in the news

Blogs on SARS-CoV-2

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for SARS-CoV-2

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [[1]]; Associate Editor(s)-in-Chief: Syed rizvi, M.B.B.S[1]

Overview

The Coronavirus disease-2019 (COVID-19), is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 forms a distinct lineage with bat SARS-like coronaviruses . The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis, that belong to the order Nidovirales, family Coronaviridae, genus Betacoronavirus, and subgenus Sarbecovirus . Coronaviruses are enveloped, single-stranded RNA viruses that can infect a wide range of hosts including avian, wild, domestic mammalian species, and humans. Coronaviruses are well known for their ability to mutate rapidly, alter tissue tropism, cross the species barrier, and adapt to different epidemiological situations. Six human coronaviruses have been reported since the 1960s; OC43, 229E, NL63, HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). First case of COVID-19 was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. On March 11, 2020 the Novel Coronavirus Disease, COVID-19, was declared a pandemic by the World Health Organization

Taxonomy

  • SARS-CoV-2 belong to the order nidovirale, family coronaviridae.[1]
  • Coronaviridae is classified into two subfamilies.
    • Torovirinae
    • Coronavirinae
  • Coronavirinae is further classified on the basis of phylogenetic analysis and genome structure into four genera:
    • Alpha coronavirus (αCoV).
    • Beta coronavirus (βCoV).
    • Gamma coronavirus (γCoV).
    • Delta coronavirus (δCoV), which contain 17, 12, 2, and 7 unique species, respectively (ICTV 2018).
  • CoV-2 falls under beta coronavirus.
Stuructural Protein Function of protein
Spike (S) Protein Critical for binding to host cell receptor (ACE-2 receptor) and facilitate entry to host cell.[2][3]
Envelope (E) Protein Envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly,

budding, envelope formation, and pathogenesis.[4]

Membrane (M) Protein Membrane (M) protein is a component of the viral envelope that plays a central role in virus

morphogenesis and assembly via its interactions with other viral proteins[5]

Nucleocapsid (N) Protein Nucleocapsid (N) protein is to package the viral RNA genome within the viral envelope into a ribonucleoprotein (RNP)

complex called the capsid.[6]


Structural Proteins

  • Envelope (E) Protein[4]
    • The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis.[10]
    • Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins.[11]
    • Recombinant CoVs lacking E exhibit significantly reduced viral titres, crippled viral maturation, or yield propagation incompetent progeny, demonstrating the importance of E in virus production and maturation.[12]


Structure Protein of Coronavirus [13]


  • Nucleocapsid (N) Protein[16]
    • The primary function of the nucleocapsid (N) protein is to package the viral RNA genome within the viral envelope into a ribonucleoprotein (RNP) complex called the capsid.
    • Ribonucleocapsid packaging is a fundamental part of viral self-assembly and replication.
    • Additionally, the N-protein of the SARS-CoV-2 affects host cell responses and may serve regulatory roles during its viral life cycle.

CORONA VIRUS LIFE CYCLE:

CORONA[17] VIRUS LIFECYCLE

Attachment and Entry:

  • The attachment of the virion to the host cell is associated with the interactions between the S protein and its receptor.
  • The sites of receptor binding domains (RBD) within the S1 region of a coronavirus (SARS-CoV-2) S protein is at the C Terminus.[18]
  • SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as their receptor[19]
  • After binding to the receptor, the virus next step is to gain access to the host cell cytosol.
  • This is generally done by cathepsin,TMPRRS2 or some other protease. This is followed by fusion of the viral and cellular membranes.
  • S protein cleavage occurs at two sites within the S2 portion of the protein, with the first cleavage important for separating the RBD (Receptor binding domain) and fusion domains of the S protein [20] and the second for exposing the fusion peptide (cleavage at S2′).
  • Fusion occurs within acidified endosomes.
  • Cleavage at S2′ exposes a fusion peptide that inserts into the membrane, which is followed by joining of two heptad repeats in S2 forming an antiparallel six-helix bundle[21].The formation of this bundle allows for the mixing of viral and cellular membranes, resulting in fusion and ultimately release of the viral genome into the cytoplasm.

RNA Replicase Protein Expression:

  • The next step in the coronavirus lifecycle is translation and assembly of the viral replicase complexes from the virion genomic RNA.

Replication and Transcription:

  • The translation and assembly of the viral replicase complexes is followed by viral RNA synthesis.
  • Viral RNA synthesis produces both genomic and sub-genomic RNAs.
  • Sub-genomic RNAs serve as mRNAs for the structural and accessory genes which reside downstream of the replicase polyproteins. All positive-sense sub-genomic RNAs are 3′ co-terminal with the full-length viral genome and thus form a set of nested RNAs, a distinctive property of the order Nidovirales. Both genomic and sub-genomic RNAs are produced through negative-sense intermediates. These negative-strand intermediates are only about 1 % as abundant as their positive-sense counterparts and contain both poly-uridylate and anti-leader sequences.[22]

Assembly and Release:

  • After replication and transcription, the structural proteins of virus ( S,M,E) are translated and then inserted into endoplasmic reticulum. From endoplasmic reticulum they are taken to endoplasmic reticulum-Golgi intermediate compartment.[23]
  • Here the N protein encapsidate the viral genome, and bud into membranes of the endoplasmic reticulum-Golgi intermediate compartment containing viral structural proteins, thus forming mature virion.[24]
  • Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

Tropism


Natural Reservoir

  • Current evidences suggest that the evolutional origin of SARS-CoV-2 is from bat virus an intermediate host between bats and human might exist.[29][30]
  • Potential intermediate host for SARS-CoV-2 can be pangolin.
  • Novel coronaviruses representing two sub-lineages related to SARS-CoV-2 were found in the samples of malytan pangolins.[31]
  • The similarity of SARS-CoV-2 to these identified coronaviruses from pangolins is approximately 85.5% to 92.4% in genomes, lower than that to the bat coronavirus RaTG13 (96.2%) 14,62.
  • However, the receptor-binding domain of S protein from one sub-lineage of the pangolin coronaviruses shows 97.4% similarity in amino acid sequences to that of SARS-CoV-2, even higher than that to RaTG13 (89.2%).[32]

References

  1. ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
  2. ↑ 2.0 2.1 Mathewson, Alison C.; Bishop, Alexandra; Yao, Yongxiu; Kemp, Fred; Ren, Junyuan; Chen, Hongying; Xu, Xiaodong; Berkhout, Ben; van der Hoek, Lia; Jones, Ian M. (2008). "Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2". Journal of General Virology. 89 (11): 2741–2745. doi:10.1099/vir.0.2008/003962-0. ISSN 0022-1317.
  3. ↑ 3.0 3.1 Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (November 2003). "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus". Nature. 426 (6965): 450–4. doi:10.1038/nature02145. PMC 7095016 Check |pmc= value (help). PMID 14647384.
  4. ↑ 4.0 4.1 Schoeman, Dewald; Fielding, Burtram C. (2019). "Coronavirus envelope protein: current knowledge". Virology Journal. 16 (1). doi:10.1186/s12985-019-1182-0. ISSN 1743-422X.
  5. ↑ 5.0 5.1 Fehr, Anthony R.; Perlman, Stanley (2015). "Coronaviruses: An Overview of Their Replication and Pathogenesis". 1282: 1–23. doi:10.1007/978-1-4939-2438-7_1. ISSN 1064-3745.
  6. ↑ McBride R, van Zyl M, Fielding BC (August 2014). "The coronavirus nucleocapsid is a multifunctional protein". Viruses. 6 (8): 2991–3018. doi:10.3390/v6082991. PMC 4147684. PMID 25105276.
  7. ↑ Mathewson, Alison C.; Bishop, Alexandra; Yao, Yongxiu; Kemp, Fred; Ren, Junyuan; Chen, Hongying; Xu, Xiaodong; Berkhout, Ben; van der Hoek, Lia; Jones, Ian M. (2008). "Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2". Journal of General Virology. 89 (11): 2741–2745. doi:10.1099/vir.0.2008/003962-0. ISSN 0022-1317.
  8. ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
  9. ↑ Nieva, José; Carrasco, Luis (2015). "Viroporins: Structures and functions beyond cell membrane permeabilization". Viruses. 7 (10): 5169–5171. doi:10.3390/v7102866. ISSN 1999-4915.
  10. ↑ Schoeman, Dewald; Fielding, Burtram C. (2019). "Coronavirus envelope protein: current knowledge". Virology Journal. 16 (1). doi:10.1186/s12985-019-1182-0. ISSN 1743-422X.
  11. ↑ Schoeman, Dewald; Fielding, Burtram C. (2019). "Coronavirus envelope protein: current knowledge". Virology Journal. 16 (1). doi:10.1186/s12985-019-1182-0. ISSN 1743-422X.
  12. ↑ Schoeman, Dewald; Fielding, Burtram C. (2019). "Coronavirus envelope protein: current knowledge". Virology Journal. 16 (1). doi:10.1186/s12985-019-1182-0. ISSN 1743-422X.
  13. ↑ Seah, Ivan; Su, Xinyi; Lingam, Gopal (2020). "Revisiting the dangers of the coronavirus in the ophthalmology practice". Eye. 34 (7): 1155–1157. doi:10.1038/s41433-020-0790-7. ISSN 0950-222X.
  14. ↑ Siu, Y. L.; Teoh, K. T.; Lo, J.; Chan, C. M.; Kien, F.; Escriou, N.; Tsao, S. W.; Nicholls, J. M.; Altmeyer, R.; Peiris, J. S. M.; Bruzzone, R.; Nal, B. (2008). "The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles". Journal of Virology. 82 (22): 11318–11330. doi:10.1128/JVI.01052-08. ISSN 0022-538X.
  15. ↑ Tooze J, Tooze S, Warren G (March 1984). "Replication of coronavirus MHV-A59 in sac- cells: determination of the first site of budding of progeny virions". Eur. J. Cell Biol. 33 (2): 281–93. PMID 6325194.
  16. ↑ McBride R, van Zyl M, Fielding BC (August 2014). "The coronavirus nucleocapsid is a multifunctional protein". Viruses. 6 (8): 2991–3018. doi:10.3390/v6082991. PMC 4147684. PMID 25105276.
  17. ↑ "The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms". |first1= missing |last1= in Authors list (help)
  18. ↑ Kubo H, Yamada YK, Taguchi F (September 1994). "Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein". J. Virol. 68 (9): 5403–10. PMC 236940. PMID 7520090.
  19. ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
  20. ↑ Belouzard S, Chu VC, Whittaker GR (April 2009). "Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites". Proc. Natl. Acad. Sci. U.S.A. 106 (14): 5871–6. doi:10.1073/pnas.0809524106. PMC 2660061. PMID 19321428.
  21. ↑ Knuhtsen S, Holst JJ, Schwartz TW, Jensen SL, Nielsen OV (May 1987). "The effect of gastrin-releasing peptide on the endocrine pancreas". Regul. Pept. 17 (5): 269–76. doi:10.1016/0167-0115(87)90284-9. PMID 2885899.
  22. ↑ Sethna PB, Hofmann MA, Brian DA (January 1991). "Minus-strand copies of replicating coronavirus mRNAs contain antileaders". J. Virol. 65 (1): 320–5. PMC 240520. PMID 1985203.
  23. ↑ Krijnse-Locker J, Ericsson M, Rottier PJ, Griffiths G (January 1994). "Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step". J. Cell Biol. 124 (1–2): 55–70. doi:10.1083/jcb.124.1.55. PMC 2119890. PMID 8294506.
  24. ↑ de Haan CA, Rottier PJ (2005). "Molecular interactions in the assembly of coronaviruses". Adv. Virus Res. 64: 165–230. doi:10.1016/S0065-3527(05)64006-7. PMC 7112327 Check |pmc= value (help). PMID 16139595.
  25. ↑ Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J (March 2020). "SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients". N. Engl. J. Med. 382 (12): 1177–1179. doi:10.1056/NEJMc2001737. PMC 7121626 Check |pmc= value (help). PMID 32074444 Check |pmid= value (help).
  26. ↑ Zheng J (2020). "SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat". Int. J. Biol. Sci. 16 (10): 1678–1685. doi:10.7150/ijbs.45053. PMC 7098030 Check |pmc= value (help). PMID 32226285 Check |pmid= value (help).
  27. ↑ Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB (May 2020). "Multiorgan and Renal Tropism of SARS-CoV-2". N. Engl. J. Med. doi:10.1056/NEJMc2011400. PMC 7240771 Check |pmc= value (help). PMID 32402155 Check |pmid= value (help).
  28. ↑ Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB (May 2020). "Multiorgan and Renal Tropism of SARS-CoV-2". N. Engl. J. Med. doi:10.1056/NEJMc2011400. PMC 7240771 Check |pmc= value (help). PMID 32402155 Check |pmid= value (help).
  29. ↑ Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W (February 2020). "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding". Lancet. 395 (10224): 565–574. doi:10.1016/S0140-6736(20)30251-8. PMC 7159086 Check |pmc= value (help). PMID 32007145 Check |pmid= value (help).
  30. ↑ Wu, Fan; Zhao, Su; Yu, Bin; Chen, Yan-Mei; Wang, Wen; Song, Zhi-Gang; Hu, Yi; Tao, Zhao-Wu; Tian, Jun-Hua; Pei, Yuan-Yuan; Yuan, Ming-Li; Zhang, Yu-Ling; Dai, Fa-Hui; Liu, Yi; Wang, Qi-Min; Zheng, Jiao-Jiao; Xu, Lin; Holmes, Edward C.; Zhang, Yong-Zhen (2020). "A new coronavirus associated with human respiratory disease in China". Nature. 579 (7798): 265–269. doi:10.1038/s41586-020-2008-3. ISSN 0028-0836.
  31. ↑ Lam, Tommy Tsan-Yuk; Shum, Marcus Ho-Hin; Zhu, Hua-Chen; Tong, Yi-Gang; Ni, Xue-Bing; Liao, Yun-Shi; Wei, Wei; Cheung, William Yiu-Man; Li, Wen-Juan; Li, Lian-Feng; Leung, Gabriel M; Holmes, Edward C.; Hu, Yan-Ling; Guan, Yi (2020). doi:10.1101/2020.02.13.945485. Missing or empty |title= (help)
  32. ↑ Lam, Tommy Tsan-Yuk; Shum, Marcus Ho-Hin; Zhu, Hua-Chen; Tong, Yi-Gang; Ni, Xue-Bing; Liao, Yun-Shi; Wei, Wei; Cheung, William Yiu-Man; Li, Wen-Juan; Li, Lian-Feng; Leung, Gabriel M; Holmes, Edward C.; Hu, Yan-Ling; Guan, Yi (2020). doi:10.1101/2020.02.13.945485. Missing or empty |title= (help)


Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=SARS-CoV-2&oldid=1629877"