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Supplementary Materials: The following are available online at http://www.mdpi.com/1999-4915/12/3/254/s1, Figure S1: Fraction of mutations in the observed sequences of the structural proteins of the three coronaviruses, Figure S2: Location of identified T cell epitopes on the SAR...

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies.

VIRUSES-BASEL, no. 3 (2020): 254

Cited by: 8|Views194
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Abstract

The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-Co...More

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Introduction
  • The ongoing outbreak of COVID-19 in the Chinese city of Wuhan (Hubei province) [1] and its alarmingly quick transmission to 25 other countries across the world [2] resulted in the World Health Organization (WHO) declaring a global health emergency on 30 January 2020 [3].
  • Coronaviruses are positive-sense single-stranded RNA viruses belonging to the family Coronaviridae
  • These viruses mostly infect animals, including birds and mammals.
  • Some recent human coronavirus infections have resulted in lethal endemics, which include the SARS
Highlights
  • The ongoing outbreak of COVID-19 in the Chinese city of Wuhan (Hubei province) [1] and its alarmingly quick transmission to 25 other countries across the world [2] resulted in the World Health Organization (WHO) declaring a global health emergency on 30 January 2020 [3]
  • Among the 115 T cell epitopes that were determined by positive T cell assays (Table 1), we found that 27 epitope-sequences were identical within SARS-CoV-2 proteins and comprised no mutation in the available SARS-CoV-2 sequences (Table 2)
  • The quest for a vaccine against the novel SARS-CoV-2 is recognized as an urgent problem
  • There is a lack of information about specific immune responses against SARS-CoV-2, which presents a challenge for vaccine development
  • Despite having limited understanding of how the human immune system responds naturally to SARS-CoV-2, these epitopes are motivated by responses they have recorded in SARS-CoV, and the fact that they map identically to SARS-CoV-2, based on the available sequence data
  • We found that only 23% and 16% of known SARS-CoV T cell and B cell epitopes map identically to SARS-CoV-2, respectively, and with no mutation having been observed in these epitopes among the available SARS-CoV-2 sequences
Methods
  • The authors excluded sequences that likely had spurious mutations resulting from sequencing errors, as indicated in the comment field of the GISAID data.
  • These nucleotide sequences were aligned to the GenBank reference sequence and translated into amino acid residues according to the coding sequence positions provided along the reference sequence for SARS-CoV-2 proteins.
  • Reference protein sequences for SARS-CoV and MERS-CoV were obtained following the same procedure from GenBank using the accession IDs NC_004718.3 and NC_019843.3, respectively
Results
  • Structural Proteins of SARS-CoV-2 Are Genetically Similar to SARS-CoV, but Not to MERS-CoV.
  • SARS-CoV-2 has been observed to be close to SARS-CoV—much more so than MERS-CoV—based on full-length genome phylogenetic analysis [9,12].
  • The authors checked whether this is true at the level of the individual structural proteins (S, E, M, and N).
  • It is noteworthy that while MERS-CoV is the more recent coronavirus to have infected humans, and is comparatively more recurrent, SARS-CoV-2 is closer to SARS-CoV, which has not been observed since 2004
Conclusion
  • The quest for a vaccine against the novel SARS-CoV-2 is recognized as an urgent problem.
  • Much remains to be learnt about the virus, its biological properties, epidemiology, etc
  • At this early stage, there is a lack of information about specific immune responses against SARS-CoV-2, which presents a challenge for vaccine development.
  • Despite having limited understanding of how the human immune system responds naturally to SARS-CoV-2, these epitopes are motivated by responses they have recorded in SARS-CoV, and the fact that they map identically to SARS-CoV-2, based on the available sequence data
  • This important observation should not be taken for granted.
  • This provides a strong indication of their potential for eliciting a robust T cell or antibody response in SARS-CoV-2
Tables
  • Table1: Filtering criteria and corresponding number of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-derived epitopes obtained from the Virus Pathogen Database and Analysis Resource (ViPR) database
  • Table2: SARS-CoV-derived T cell epitopes obtained using positive T cell assays that are identical in SARS-CoV-2 (27 epitopes in total)
  • Table3: Set of the SARS-CoV-derived spike (S) and nucleocapsid (N) protein T cell epitopes (obtained from positive MHC binding assays) that are identical in SARS-CoV-2 and that maximize estimated population coverage globally (87 distinct epitopes)
  • Table4: SARS-CoV-derived linear B cell epitopes from S (23; 20 of which are located in subunit S2) and N (22) proteins that are identical in SARS-CoV-2 (45 epitopes in total)
  • Table5: SARS-CoV-derived discontinuous B cell epitopes (and associated known antibodies [<a class="ref-link" id="c39" href="#r39">39</a>,<a class="ref-link" id="c40" href="#r40">40</a>,<a class="ref-link" id="c41" href="#r41">41</a>]) that have at least one site with an identical amino acid to the corresponding site in SARS-CoV-2
Download tables as Excel
Funding
  • M.R.M. and A.A.Q. were supported by the General Research Fund of the Hong Kong Research Grants Council (RGC) [Grant No 16204519]
  • S.F.A. was supported by the Hong Kong Ph.D
Study subjects and analysis
cases: 8098
SARS-CoV originated from Southern China and caused an endemic in 2003. A total of 8098 cases of SARS were reported globally, including 774 associated deaths, and an estimated case-fatality rate of 14%–15% [10]. The first case of MERS occurred in Saudi Arabia in 2012

cases: 2494
The first case of MERS occurred in Saudi Arabia in 2012. Since then, a total of 2,494 cases of infection have been reported, including 858 associated deaths, and an estimated high case-fatality rate of 34.4% [11]. While no case of SARS-CoV infection has been reported since 2004, MERS-CoV has been around since 2012 and has caused multiple sporadic outbreaks in different countries

structural proteins: 4
SARS-CoV-derived discontinuous B cell epitopes (and associated known antibodies [39,40,41]) that have at least one site with an identical amino acid to the corresponding site in SARS-CoV-2. Comparison of the similarity of structural proteins of SARS-CoV-2 with the corresponding proteins of SARS-CoV and MERS (Middle East Respiratory Syndrome)-CoV. (a) Percentage genetic similarity of the individual structural proteins of SARS-CoV-2 with those of SARS-CoV and MERS-CoV. The reference sequence of each coronavirus (Materials and Methods) was used to calculate the percentage genetic similarity. (b) Circular phylogram of the phylogenetic trees of the four structural proteins. All trees were constructed based on the available unique sequences using PASTA [31] and rooted with the outgroup Zaria Bat CoV strain (accession ID: HQ166910.1). Location of SARS-CoV S protein subunits and SARS-CoV-derived B cell epitopes on the proteiFnigsutrreuc2t.urLeo(cPatDioBn IoDf S: A5XRSL‐RC)o.V(aS) pSruobteuinnistusbSu1niatsnadndS2SAarReS‐iCnodVic‐adteerdiveind Bpucerlpl leepiatnopdesgroenetnhecolor, respecptriovteeliny. sTtrhuecturerece(pPtDoBr bIDin: d5XinLgR)m. (oat)ifSulibeusnwitisthS1inatnhdeSS21asrue binudniictataenddinispiunrdpilceaatendd ignreoernacnogloerc, olor. (b) Rerseisdpueecstivoeflyth. eThlienereacreBptcoerlbl ienpdiitnogpemso, ttihf alitews weriethiidnetnhteicSa1l sinubSuAnRitSa-nCdoiVs-i2nd(Ticaabtleed4i)n, aorreansgheocwonlorin. red color.(rbeTd)hRceoedsloiadrr.ukTehsaenofddtahlriekglhainntdesahlriagBdhcteesrlhleaefldpeeictroteptfhelesec,tsthtuharetfawsuceerrfeaacnieddeannbtduicrbaiuleridnierdSeAsreRidsSiud‐Ceuose,Vs,r‐er2es(spTpeaecbcttlieivv4ee)ll,yya..r((ecc)s)LhLooocwacntaiotiinnon of disconotfinduisocounstiBnuceolulseBpicteolpl eespitthoaptesshthaaret sahtalreeasatt olenaestidonene tiidceanltriecaslidreuseidwuiethwcitohrrceosrpreosnpdonindginSgASRASR-SC‐oV-2 sites (CTaobVl‐e2 5s)it.eIsd(eTnatbilcea5l)e. pIditeonptiecarleespidituoepse areresidshuoeswanreinshroewdncoinlorre,dwcholioler,twhehirleemthaeinreimngaienpinitgoeppeitroepseidues are shroewsidnuiens barleueshcoowlonr.inBboltuhe tchoelosri.dBeotvhiethwe (sliedfet pvaienwel)(laefnt dpatnheel) taonpd vthieewto(privgihewt p(arnigehl)t opafntehl)eosftrthuecture are shsotrwunct.ure are shown

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Syed Faraz Ahmed
Syed Faraz Ahmed
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