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'''For the main page on coronavirus infection, please click [[Coronavirus|here]]'''<br>
<br />
==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  <ref name="ZhouYang20202">{{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>. Coronaviruses are [[Enveloped virus|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.<ref name="pmid20031041">{{cite journal |vauthors=Decaro N, Mari V, Elia G, Addie DD, Camero M, Lucente MS, Martella V, Buonavoglia C |title=Recombinant canine coronaviruses in dogs, Europe |journal=Emerging Infect. Dis. |volume=16 |issue=1 |pages=41–7 |date=January 2010 |pmid=20031041 |pmc=2874359 |doi=10.3201/eid1601.090726 |url=}}</ref> 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
<br />
==Taxonomy ==


The '''novel coronavirus''' ('''SARS-CoV-2'''),<ref>{{Cite web |url= https://www.who.int/publications-detail/surveillance-case-definitions-for-human-infection-with-novel-coronavirus-(ncov) |title=Surveillance case definitions for human infection with novel coronavirus (nCoV) |publisher=World Health Organization |accessdate=21 January 2020}}</ref><ref>{{cite web |url=https://www.cdc.gov/coronavirus/novel-coronavirus-2019.html |title=Novel coronavirus (2019-nCoV), Wuhan, China |date=10 January 2020 |publisher=[[Centers for Disease Control and Prevention]] |location=United States |url-status=live |accessdate=16 January 2020}}</ref> also known as the '''Wuhan coronavirus''',<ref name="Fox2020" /> 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]].<ref>{{Cite web|url=http://www.dph.illinois.gov/topics-services/diseases-and-conditions/diseases-a-z-list/coronavirus/faq|title=2019 Novel Coronavirus (2019 nCoV): Frequently Asked Questions {{!}} IDPH|website=www.dph.illinois.gov|access-date=2020-01-27}}</ref> [[Genomic sequencing]] has shown that it is a [[Positive-sense single-stranded RNA virus|positive-sense, single-stranded RNA]] [[coronavirus]].<ref>{{cite web|url=http://www.chinacdc.cn/dfdt/201912/t20191226_209404.html|title=中国疾病预防控制中心|publisher=[[Chinese Center for Disease Control and Prevention]]|location=People's Republic of China|language=Chinese|accessdate=9 January 2020}}</ref><ref name=":0">{{cite web|url=http://www.xinhuanet.com/english/2020-01/09/c_138690570.htm|title=New-type coronavirus causes pneumonia in Wuhan: expert|location=People's Republic of China|accessdate=9 January 2020|agency=Xinhua}}</ref><ref name=":1">{{cite web|url=https://platform.gisaid.org/epi3/start/CoV2020|title=CoV2020|website=platform.gisaid.org|url-status=live|accessdate=12 January 2020}}</ref>
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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.<ref>http://www.nj.gov/health/cd/documents/topics/NCOV/NCoV_LINCS_wuhan_update_011820_combined.pdf</ref> Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to [[SARS-CoV]] (79.5%)<ref name=":2">{{Cite journal|url=https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2|title=Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin|first1=Peng|last1=Zhou|first2=Xing-Lou|last2=Yang|first3=Xian-Guang|last3=Wang|first4=Ben|last4=Hu|first5=Lei|last5=Zhang|first6=Wei|last6=Zhang|first7=Hao-Rui|last7=Si|date=23 January 2020|journal=bioRxiv|pages=2020.01.22.914952|via=www.biorxiv.org|doi=10.1101/2020.01.22.914952}}</ref> and bat coronaviruses (96%),<ref name=":2" /> with a likely origin in bats being theorized.<ref name=":3" /><ref name=":4" /><ref>{{Cite journal|last=Callaway|first=Ewen|last2=Cyranoski|first2=David|date=2020-01-23|title=Why snakes probably aren’t spreading the new China virus|url=https://www.nature.com/articles/d41586-020-00180-8|journal=Nature|language=en|doi=10.1038/d41586-020-00180-8}}</ref>
*SARS-CoV-2 belong to the order [[Nidovirales|nidovirale]], family [[coronaviridae]].
*[[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.


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


The first known human infection occurred in early December 2019. [[Molecular clock]] approaches suggest a similar, or slightly earlier, date of origin.<ref name="early">{{cite web |last1=Cohen|first1=Jon |title=Wuhan seafood market may not be source of novel virus spreading globally |url=https://www.sciencemag.org/news/2020/01/wuhan-seafood-market-may-not-be-source-novel-virus-spreading-globally |website=Science {{!}} AAAS |language=en |date=26 January 2020}}</ref>
*Coronaviruses are enveloped, icosahedral symmetric particles, approximately 80–220 nm in diameter containing a non-segmented, single-strand, positive-sense RNA genome of about 26–32 kb in size. <ref name="pmid16339739">{{cite journal |vauthors=Weiss SR, Navas-Martin S |title=Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus |journal=Microbiol. Mol. Biol. Rev. |volume=69 |issue=4 |pages=635–64 |date=December 2005 |pmid=16339739 |pmc=1306801 |doi=10.1128/MMBR.69.4.635-664.2005 |url=}}</ref>
*Corona in Latin means crown, and this name was attributed to the virus due to the presence of spike projections from the virus [[Viral envelope|envelope]] that give it the shape of a crown under the electron microscope.
* Nido means nest and refers to the ability of the viruses of this order to make a nested set of subgenomic [[mRNA]]


An outbreak of SARS-CoV-2 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.<ref>{{cite news |url= https://www.scmp.com/news/hong-kong/health-environment/article/3047310/china-coronavirus-hong-kong-widens-criteria |title=China coronavirus: Hong Kong widens criteria for suspected cases after second patient confirmed, as MTR cancels Wuhan train ticket sales |date=23 January 2020 |publisher=[[South China Morning Post]] |location=[[Hong Kong]] |accessdate=23 January 2020}}</ref><ref>{{Cite web|url=https://www.ecdc.europa.eu/en/news-events/novel-coronavirus-three-cases-reported-france|title=Novel coronavirus: three cases reported in France|date=25 January 2020|website=European Centre for Disease Prevention and Control}}</ref><ref>{{Cite news|url=https://www.theguardian.com/science/2020/jan/25/coronavirus-five-people-in-nsw-being-tested-for-deadly-disease|title=Coronavirus: three cases in NSW and one in Victoria as infection reaches Australia|last=Doherty|first=Ben|date=25 January 2020|work=The Guardian|access-date=26 January 2020|language=en-GB|issn=0261-3077}}</ref>
'''Envelope'''
====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.<ref name="GI2020Update">{{cite web |title=Operations Dashboard for ArcGIS |url=https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 |website=gisanddata.maps.arcgis.com |accessdate=28 January 2020}}</ref> 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.<ref name="WHO25thUpdate">{{cite web |title=Novel Coronavirus (2019-nCoV) SITUATION REPORT - 5 25 JANUARY 2020 |url=https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200125-sitrep-5-2019-ncov.pdf |accessdate=26 January 2020}}</ref> 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.<ref name="auto">{{Cite news |url= https://www.cbc.ca/news/health/coronavirus-human-to-human-1.5433187 |title=China confirms human-to-human transmission of new coronavirus |date=20 January 2020 |publisher=[[Canadian Broadcasting Corporation]] |accessdate=21 January 2020 |url-status=live}}</ref>
*'''Spike (S) Protein'''
** Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
**Early studies indicate that SARS-CoV-2 uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S protein priming.<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 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'''
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.<ref name="wmhc2020-01-112">{{cite web|url=http://wjw.wuhan.gov.cn/front/web/showDetail/2020011109036|title=Experts explain the latest bulletin of unknown cause of viral pneumonia|date=11 January 2020|website=Wuhan Municipal Health Commission|url-status=live|archive-url=https://web.archive.org/web/20200111031745/http://wjw.wuhan.gov.cn/front/web/showDetail/2020011109036|archive-date=11 January 2020|access-date=11 January 2020}}</ref><ref name="Hui14Jan2020">{{vcite journal|authors=Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E|title=The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China|journal=Int J Infect Dis|year=2020 Jan 14|volume=91|issue=|pages=264–266|pmid=31953166|doi=10.1016/j.ijid.2020.01.009}}{{open access}}</ref><ref>{{Cite web|url=https://www.who.int/news-room/q-a-detail/q-a-coronaviruses|title=Q&A on coronaviruses|website=www.who.int|language=en|access-date=2020-01-27}}</ref> The [[Chinese Center for Disease Control and Prevention]] (CCDC) is testing existing pneumonia treatments for efficacy in treating coronavirus-related pneumonia.<ref name="auto1">{{Cite web|url=http://www.xinhuanet.com/english/2020-01/26/c_138734908.htm|title=China CDC developing novel coronavirus vaccine|date=2020-01-26|website=Xinhua}}</ref>
**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.
**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.
**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,<ref name="thomreut_antivirals">{{Cite news|url=https://www.reuters.com/article/us-china-health-pneumonia-who-idUSKBN1ZD16J|title=WHO says new China coronavirus could spread, warns hospitals worldwide|date=14 January 2020|agency=Reuters|access-date=21 January 2020}}</ref> including [[Protease inhibitor (pharmacology)|protease inhibitors]] like [[indinavir]], [[saquinavir]], [[remdesivir]], [[lopinavir/ritonavir]] and [[interferon beta]].<ref>{{Cite journal|url=https://www.biorxiv.org/content/10.1101/2020.01.27.921627v1|title=Nelfinavir was predicted to be a potential inhibitor of 2019 nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation|first1=Zhijian|last1=Xu|first2=Cheng|last2=Peng|first3=Yulong|last3=Shi|first4=Zhengdan|last4=Zhu|first5=Kaijie|last5=Mu|first6=Xiaoyu|last6=Wang|first7=Weiliang|last7=Zhu|date=28 January 2020|journal=bioRxiv|pages=2020.01.27.921627|via=www.biorxiv.org|doi=10.1101/2020.01.27.921627}}</ref><ref name="Pau2020">{{cite journal |last1=Paules |first1=Catharine I. |last2=Marston |first2=Hilary D. |last3=Fauci |first3=Anthony S. |title=Coronavirus Infections—More Than Just the Common Cold |journal=JAMA |date=23 January 2020 |doi=10.1001/jama.2020.0757|pmid=31971553 }}</ref><ref>{{Cite news|url=https://www.reuters.com/article/gilead-coronavirus-idUSL4N29S45D|title=Gilead assessing Ebola drug as possible coronavirus treatment|date=2020-01-23|work=Reuters|access-date=2020-01-26}}</ref> The effectiveness of previously identified [[monoclonal antibodies]] (mAbs) is also under investigation.<ref>{{Cite web|url=https://www.pharmaceutical-technology.com/news/coronavirus-vir-biotechnology-novavax-vaccine/|title=Coronavirus: Vir Biotechnology and Novavax announce vaccine plans-GB|access-date=2020-01-26}}</ref>
*'''Membrane (M) Protein'''
**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.
**M is located among the S proteins in the virus envelope along with small amounts of E and is the primary driver of the 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 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>


==Virology==
*'''Nucleocapsid (N) Protein'''
===Infection===
** 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.
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]],<ref name="latent">{{cite news |title=【武漢肺炎】衛健委︰新型冠狀病毒傳播力增強　潛伏期最短僅1天 |url=https://news.mingpao.com/ins/%E5%85%A9%E5%B2%B8/article/20200126/s00004/1580028707559/%E3%80%90%E6%AD%A6%E6%BC%A2%E8%82%BA%E7%82%8E%E3%80%91%E8%A1%9B%E5%81%A5%E5%A7%94-%E6%96%B0%E5%9E%8B%E5%86%A0%E7%8B%80%E7%97%85%E6%AF%92%E5%82%B3%E6%92%AD%E5%8A%9B%E5%A2%9E%E5%BC%B7-%E6%BD%9B%E4%BC%8F%E6%9C%9F%E6%9C%80%E7%9F%AD%E5%83%851%E5%A4%A9 |work=明報新聞網|language=CN}}</ref><ref>{{Cite web|url=https://news.163.com/20/0126/16/F3R33UL80001899O.html|title=专家：病毒潜伏期有传染性 有人传染同事后才发病|date=26 January 2020|website=news.163.com|language=CN}}</ref> 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."<ref>{{Cite web|url=https://www.medpagetoday.com/infectiousdisease/publichealth/84548|title=U.S. Notches Fifth Coronavirus Case as Global Count Nears 3,000|date=27 January 2020|website=www.medpagetoday.com}}</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2020/t0127-coronavirus-update.html|title=Transcript of 2019 Novel Coronavirus (2019-nCoV) Update &#124; CDC Online Newsroom &#124; CDC|date=28 January 2020|website=www.cdc.gov}}</ref>
**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 />


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.<ref>{{Cite web|url=https://www.theatlantic.com/science/archive/2020/01/how-fast-and-far-will-new-coronavirus-spread/605632/|title=The Deceptively Simple Number Sparking Coronavirus Fears|date=28 January 2020|website=[[The Atlantic]]|language=EN}}</ref><ref>{{Cite journal|last=Liu|first=Tao|last2=Hu|first2=Jianxiong|last3=Kang|first3=Min|last4=Lin|first4=Lifeng|last5=Zhong|first5=Haojie|last6=Xiao|first6=Jianpeng|last7=He|first7=Guanhao|last8=Song|first8=Tie|last9=Huang|first9=Qiong|last10=Rong|first10=Zuhua|last11=Deng|first11=Aiping|last12=Zeng|first12=Weilin|last13=Tan|first13=Xiaohua|last14=Zeng|first14=Siqing|last15=Zhu|first15=Zhihua|last16=Li|first16=Jiansen|last17=Wan|first17=Donghua|last18=Lu|first18=Jing|last19=Deng|first19=Huihong|last20=He|first20=Jianfeng|last21=Ma|first21=Wenjun|date=2020-01-25|title=Transmission dynamics of 2019 novel coronavirus (2019-nCoV)|url=https://www.biorxiv.org/content/10.1101/2020.01.25.919787v1|journal=bioRxiv|language=en|pages=2020.01.25.919787|doi=10.1101/2020.01.25.919787}}</ref><ref>{{Cite journal|last=Zhao|first=Shi|last2=Ran|first2=Jinjun|last3=Musa|first3=Salihu Sabiu|last4=Yang|first4=Guangpu|last5=Lou|first5=Yijun|last6=Gao|first6=Daozhou|last7=Yang|first7=Lin|last8=He|first8=Daihai|date=2020-01-24|title=Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak|url=https://www.biorxiv.org/content/10.1101/2020.01.23.916395v1|journal=bioRxiv|language=en|pages=2020.01.23.916395|doi=10.1101/2020.01.23.916395}}</ref><ref>{{Cite journal|last=Read|first=Jonathan M.|last2=Bridgen|first2=Jessica RE|last3=Cummings|first3=Derek AT|last4=Ho|first4=Antonia|last5=Jewell|first5=Chris P.|date=2020-01-28|title=Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions|url=https://www.medrxiv.org/content/10.1101/2020.01.23.20018549v2|journal=medRxiv|language=en|pages=2020.01.23.20018549|doi=10.1101/2020.01.23.20018549}}</ref> 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.<ref name="Saey24Jan2020">{{Cite web|url=https://www.sciencenews.org/article/how-new-wuhan-coronavirus-stacks-up-against-sars-mers|title=How the new coronavirus stacks up against SARS and MERS|first=Tina Hesman|last=Saey|date=24 January 2020|access-date=25 January 2020|archive-url=https://web.archive.org/web/20200125064423/https://www.sciencenews.org/article/how-new-wuhan-coronavirus-stacks-up-against-sars-mers|archive-date=25 January 2020|url-status=live}}</ref>
===='''<big>Corona Virus Life Cycle</big>:'''====
===<small>Attachment and Entry</small>:===


===Reservoir===
*The attachment of the virion to the host cell is associated with the  interactions between the S protein and its receptor.
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.<ref>{{Cite news|url=https://www.nytimes.com/2020/01/25/world/asia/china-markets-coronavirus-sars.html|title=China’s Omnivorous Markets Are in the Eye of a Lethal Outbreak Once Again|last=Myers|first=Steven Lee|date=January 25, 2020|work=The New York Times|access-date=|url-status=live}}</ref> The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.<ref name="AP20.01.27">{{cite|title=China temporarily bans wildlife trade in wake of outbreak| url=https://apnews.com/d59f43a911996a729cdf8636f5aa4ce4| first1=Sam| last1=McNeil| first2=Penny Yi| last2=Wang| first3=Elaine| last3=Kurtenbach| date=2020-01-27}}</ref>
*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>
*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>
*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 <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′).
*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<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.


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. SARS-CoV-2 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 SARS-CoV-2.<ref name=":3">Sample [https://www.ncbi.nlm.nih.gov/nuccore/MG772933 CoVZC45] and [https://www.ncbi.nlm.nih.gov/nuccore/MG772934 CoVZXC21], see [https://nextstrain.org/groups/blab/sars-like-cov there for an interactive visualisation]</ref><ref name=":4">{{cite journal|title=The 2019 new Coronavirus epidemic: evidence for virus evolution|url=https://www.biorxiv.org/content/10.1101/2020.01.24.915157v1|doi=10.1101/2020.01.24.915157v1|doi-broken-date=2020-01-25}}</ref> A third unpublished virus genome from ''[[Intermediate horseshoe bat|Rhinolophus affinis]]'', "RaTG13", is said to have a 96% resemblance to SARS-CoV-2.<ref name="bioRxivBatOrigin">{{cite journal |title=Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin |url= https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2 |author=Wuhan Institue of Virology |publisher=[[bioRxiv]] |accessdate=24 January 2020 |date=23 January 2020 |doi=10.1101/2020.01.22.914952v2 |doi-broken-date=2020-01-25}} (BetaCoV/bat/Yunnan/RaTG13/2013; available on GISAID)</ref> 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.<ref>{{Cite web|url=https://nextstrain.org/flu/seasonal/h3n2/ha/2y?clade=3c3|title=Real-time tracking of influenza A/H3N2 evolution using data from GISAID
===='''RNA Replicase Protein Expression:'''====
|website=nextstrain.org}}</ref>


===Phylogenetics and taxonomy===
*The next step in the coronavirus lifecycle is translation and assembly of the viral replicase complexes  from the virion genomic RNA.
{{Infobox genome
| image      = File:2019-nCoV genome.svg
| caption    = [[Genome]] organisation (click to enlarge)
| type        = nucleotide
| taxId      = MN908947
| size        = 29,903 bases
| year        = 2020
}}
SARS-CoV-2 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]].<ref name="NEJM">{{cite journal |last1=Zhu |first1=Na |last2=Zhang |first2=Dingyu |last3=Wang |first3=Wenling |last4=Li |first4=Xinwang |last5=Yang |first5=Bo |last6=Song |first6=Jingdong |last7=Zhao |first7=Xiang |last8=Huang |first8=Baoying |last9=Shi |first9=Weifeng |last10=Lu |first10=Roujian |last11=Niu |first11=Peihua |last12=Zhan |first12=Faxian |last13=Ma |first13=Xuejun |last14=Wang |first14=Dayan |last15=Xu |first15=Wenbo |last16=Wu |first16=Guizhen |last17=Gao |first17=George F. |last18=Tan |first18=Wenjie |title=A Novel Coronavirus from Patients with Pneumonia in China, 2019 |journal=[[New England Journal of Medicine]] |location=United States |date=24 January 2020 |volume=0 |doi=10.1056/NEJMoa2001017 |issn=0028-4793}}<!--Location refers to where the publisher is from.--></ref>


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>{{cite web |url=https://nextstrain.org/groups/blab/sars-like-cov |title=Phylogeny of SARS-like betacoronaviruses |website=nextstrain |accessdate=18 January 2020}}</ref><ref name="Hui14Jan2020" /><ref name="Wong2019">{{vcite journal |authors=Antonio C. P. Wong, Xin Li, Susanna K. P. Lau, Patrick C. Y. Woo |pmc=6409556 |title=Global Epidemiology of Bat Coronaviruses |journal=Viruses |year=2019 Feb |volume=11 |issue=2 |pages=174 |doi=10.3390/v11020174}}</ref> Its [[RNA]] sequence is approximately 30 [[Base pair#Length measurements|kb]] in length.<ref name=":1" />
<br />
==== Replication and Transcription:====


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" /><ref>{{cite web |url= http://virological.org/t/initial-genome-release-of-novel-coronavirus/319 |title=Initial genome release of novel coronavirus |date=11 January 2020 |website=Virological |accessdate=12 January 2020}}</ref><ref>{{Cite journal |date=17 January 2020 |title=Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome |url= http://www.ncbi.nlm.nih.gov/nuccore/MN908947.3 |journal=[[National Center for Biotechnology Information]] |publisher=National Institutes of Health |location=United States}}</ref> 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.<ref>{{Cite web|url=https://nextstrain.org/ncov|title=Genomic epidemiology of novel coronavirus (nCoV) using data generated by Fudan University, China CDC, Chinese Academy of Medical Sciences, Chinese Academy of Sciences, Zhejiang Provincial Center for Disease Control and Prevention and the Thai National Institute of Health shared via GISAID|last1=Bedford|first1=Trevor|last2=Neher|first2=Richard|date=|website=nextstrain.org|url-status=live|archive-url=|archive-date=|accessdate=26 January 2020}}</ref>
*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-strand 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.<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>
=== Structural biology ===
[[File:Coronavirus 2019-nCoV.3.png|thumb|right|Innophore [[Phyre2]] [[ribbon diagram]] of the SARS-CoV-2 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.<ref>{{cite journal |title=Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission |url= http://engine.scichina.com/publisher/scp/journal/SCLS/doi/10.1007/s11427-020-1637-5 |journal=SCIENCE CHINA Life Sciences |doi=10.1007/s11427-020-1637-5 |doi-broken-date=2020-01-24 |accessdate=23 January 2020}}<!-- Broken DOI --></ref> 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 SARS-CoV-2.<ref>{{cite journal |last1=Letko |first1=Michael |last2=Munster |first2=Vincent |date=22 January 2020 |title=Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV |url= https://www.biorxiv.org/content/10.1101/2020.01.22.915660v1 |journal=BiorXiv |doi=10.1101/2020.01.22.915660 |accessdate=24 January 2020}}</ref><ref>{{cite journal |last1=Zhou |first1=Peng |last2=Shi |first2=Zheng-Li |date=2020 |title=Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin |url=https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2 |journal=BiorXiv |doi=10.1101/2020.01.22.914952 |accessdate=24 January 2020}}</ref><ref>{{cite journal |last1=Gralinski |first1=Lisa E. |last2=Menachery |first2=Vineet D. |date=2020 |title=Return of the Coronavirus: 2019-nCoV |journal=Viruses |volume=12 |issue=2 |pages=135 |doi=10.3390/v12020135}}</ref>
 
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,<ref name="inno-dock">{{cite journal |url=https://innophore.com/2019-ncov/ |title=Wuhan coronavirus 2019-nCoV - what we can find out on a structural bioinformatics level |last1=Gruber |first1=Christian |last2=Steinkellner |first2=Georg |date=23 January 2020 |website=Innophore Enzyme Discovery |publisher=Innophore GmbH |doi=10.6084/m9.figshare.11752749}}</ref> and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant SARS-CoV-2 protease.<ref name="cas-dock">{{cite web |title=上海药物所和上海科技大学联合发现一批可能对新型肺炎有治疗作用的老药和中药 |url=http://www.cas.cn/syky/202001/t20200125_4732909.shtml |website=Chinese Academy of Sciences |date=2020-01-25}}</ref><!-- Authors are Rao ZH, Yang HT; check PDB daily -->
 
== Vaccine research ==
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" /><ref>{{Cite web|url=https://www.scmp.com/news/china/society/article/3047676/number-coronavirus-cases-china-doubles-spread-rate-accelerates|title=Chinese scientists race to develop vaccine as coronavirus death toll jumps|date=2020-01-26|website=SCMP}}</ref> 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.<ref>{{cite news |last1=Cheung |first1=Elizabeth |title=Hong Kong researchers have developed coronavirus vaccine, expert reveals |url=https://www.scmp.com/news/hong-kong/health-environment/article/3047956/china-coronavirus-hong-kong-researchers-have |work=South China Morning Post |date=28 January 2020 |language=en}}</ref>
 
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" />
 
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.<ref>{{Cite web|url=https://ca.news.yahoo.com/saskatchewan-lab-joins-global-effort-090415232.html|title=Saskatchewan lab joins global effort to develop coronavirus vaccine|website=ca.news.yahoo.com}}</ref> 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" />


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

Revision as of 04:25, 1 July 2020


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 [1]. 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.[2] 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.
  • 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.

Biology

Structure

  • Coronaviruses are enveloped, icosahedral symmetric particles, approximately 80–220 nm in diameter containing a non-segmented, single-strand, positive-sense RNA genome of about 26–32 kb in size. [3]
  • Corona in Latin means crown, and this name was attributed to the virus due to the presence of spike projections from the virus envelope that give it the shape of a crown under the electron microscope.
  • Nido means nest and refers to the ability of the viruses of this order to make a nested set of subgenomic mRNA

Envelope

Structural Proteins

  • Spike (S) Protein
    • Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
    • Early studies indicate that SARS-CoV-2 uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S protein priming.[4]
    • The spike (S) glycoprotein is a type I 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.[5]
  • Envelope (E) Protein
    • 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.
    • 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.
    • 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.[6]
  • Membrane (M) Protein
    • 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.
    • M is located among the S proteins in the virus envelope along with small amounts of E and is the primary driver of the 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 humoral response which suggests it could serve as a potential target in vaccine design.[7] [8]
  • Nucleocapsid (N) Protein
    • 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:

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.[9]
  • SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as their receptor[10]
  • 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 [11] 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[12].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-strand 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.[13]

Tropism


Natural Reservoir


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. ↑ Decaro N, Mari V, Elia G, Addie DD, Camero M, Lucente MS, Martella V, Buonavoglia C (January 2010). "Recombinant canine coronaviruses in dogs, Europe". Emerging Infect. Dis. 16 (1): 41–7. doi:10.3201/eid1601.090726. PMC 2874359. PMID 20031041.
  3. ↑ Weiss SR, Navas-Martin S (December 2005). "Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus". Microbiol. Mol. Biol. Rev. 69 (4): 635–64. doi:10.1128/MMBR.69.4.635-664.2005. PMC 1306801. PMID 16339739.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.


References

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