PMID- 33828922
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240331
IS  - 2167-8359 (Print)
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 9
DP  - 2021
TI  - Immunoinformatic approach to design a multiepitope vaccine targeting 
      non-mutational hotspot regions of structural and non-structural proteins of the 
      SARS CoV2.
PG  - e11126
LID - 10.7717/peerj.11126 [doi]
LID - e11126
AB  - BACKGROUND: The rapid Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) 
      outbreak caused severe pandemic infection worldwide. The high mortality and 
      morbidity rate of SARS CoV2 is due to the unavailability of vaccination and 
      mutation in this virus. The present article aims to design a potential vaccine 
      construct VTC3 targeting the non-mutational region of structural and 
      non-structural proteins of SARS CoV2. METHODS: In this study, vaccines were 
      designed using subtractive proteomics and reverse vaccinology. To target the 
      virus adhesion and evasion, 10 different structural and non-structural proteins 
      have been selected. Shortlisted proteins have been screened for B cell, T cell 
      and IFN gamma interacting epitopes. 3D structure of vaccine construct was modeled 
      and evaluated for its physicochemical properties, immunogenicity, allergenicity, 
      toxicity and antigenicity. The finalized construct was implemented for docking 
      and molecular dynamics simulation (MDS) with different toll-like receptors (TLRs) 
      and human leukocyte antigen (HLA). The binding energy and dissociation construct 
      of the vaccine with HLA and TLR was also calculated. Mutational sensitivity 
      profiling of the designed vaccine was performed, and mutations were reconfirmed 
      from the experimental database. Antibody production, clonal selection, antigen 
      processing, immune response and memory generation in host cells after injection 
      of the vaccine was also monitored using immune simulation. RESULTS: Subtractive 
      proteomics identified seven (structural and non-structural) proteins of this 
      virus that have a role in cell adhesion and infection. The different epitopes 
      were predicted, and only extracellular epitopes were selected that do not have 
      similarity and cross-reactivity with the host cell. Finalized epitopes of all 
      proteins with minimum allergenicity and toxicity were joined using linkers to 
      designed different vaccine constructs. Docking different constructs with 
      different TLRs and HLA demonstrated a stable and reliable binding affinity of 
      VTC3 with the TLRs and HLAs. MDS analysis further confirms the interaction of 
      VTC3 with HLA and TLR1/2 complex. The VTC3 has a favorable binding affinity and 
      dissociation constant with HLA and TLR. The VTC3 does not have similarities with 
      the human microbiome, and most of the interacting residues of VTC3 do not have 
      mutations. The immune simulation result showed that VTC3 induces a strong immune 
      response. The present study designs a multiepitope vaccine targeting the 
      non-mutational region of structural and non-structural proteins of the SARS CoV2 
      using an immunoinformatic approach, which needs to be experimentally validated.
CI  - (c) 2021 Solanki et al.
FAU - Solanki, Vandana
AU  - Solanki V
AD  - Department of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, 
      India.
FAU - Tiwari, Monalisa
AU  - Tiwari M
AUID- ORCID: 0000-0002-3124-5225
AD  - Department of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, 
      India.
FAU - Tiwari, Vishvanath
AU  - Tiwari V
AUID- ORCID: 0000-0003-1664-3871
AD  - Department of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, 
      India.
LA  - eng
PT  - Journal Article
DEP - 20210323
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
PMC - PMC7996071
OTO - NOTNLM
OT  - Envelope protein
OT  - Membrane proteins
OT  - Multiepitope vaccine
OT  - ORF1ab polyprotein
OT  - ORF3a protein
OT  - ORF8 protein
OT  - SARS CoV2
OT  - Surface glycoprotein
COIS- The authors declare that they have no competing interests.
EDAT- 2021/04/09 06:00
MHDA- 2021/04/09 06:01
PMCR- 2021/03/23
CRDT- 2021/04/08 06:30
PHST- 2020/12/01 00:00 [received]
PHST- 2021/02/26 00:00 [accepted]
PHST- 2021/04/08 06:30 [entrez]
PHST- 2021/04/09 06:00 [pubmed]
PHST- 2021/04/09 06:01 [medline]
PHST- 2021/03/23 00:00 [pmc-release]
AID - 11126 [pii]
AID - 10.7717/peerj.11126 [doi]
PST - epublish
SO  - PeerJ. 2021 Mar 23;9:e11126. doi: 10.7717/peerj.11126. eCollection 2021.