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Immunoinformatic paradigm predicts macrophage and T-cells epitope responses against globally conserved spike fragments of SARS CoV-2 for universal vaccination.
Maiti, Smarajit; Banerjee, Amrita; Santra, Dipannita; Kanwar, Mehak.
  • Maiti S; Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Midnapore, India; Agricure Biotech Research Society, Epidemiology and Human Health Division, Midnapore 721 101, India. Electronic address: maitism@rediffmail.com.
  • Banerjee A; Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Midnapore, India. Electronic address: bamrita.bioinfo@gmail.com.
  • Santra D; Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Midnapore, India.
  • Kanwar M; Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Midnapore, India.
Int Immunopharmacol ; 108: 108847, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1851320
ABSTRACT

BACKGROUND:

Different quickly-developed vaccines are introduced against COVID-19 with inconclusive results especially against some recent variants. Eventually, somewhere COVID-19 cases decline and in some countries it revived with some new mutant-variants (i.e. D614G, Delta and Omicron).

OBJECTIVES:

Proposing a universal vaccination strategy by screening globally-conserved SARS-CoV-2 spike-epitopes.

METHODS:

Presently, several conserved (186-countries) sequences including multiple-variants (ClustalX2) epitopic-regions (SVMTriP and IEDB) and in-silico mutants of SARS-CoV-2 spike-protein-fragments (Cut1-4) were screened for their stability against proteases, antigenicity (VaxiJen V2.0 and for glycosylation effects NetOGlyc-NetNGlyc), MHCI/II reactivity (IEDB-TOOLS) and CD4+ responses by molecular-docking (Haddock2.4/PatchDock). We also examined Molecular-Dynamic-Simulation (myPresto verson-5) of MHC-II 3LQZ with 3-Cuts and T-cell 2-molecules (1KGC/4JRX) with SM3-Cut. The MD-simulation was run with 5000-cycles after 300 k-heating/1-atm pressure adjustment for the system-equilibration. Finally, 1000 fs production was run.

RESULTS:

The cut4-mutant (SRLFRKSNLKPFERD) showed the highest combined-score 48.23548 and Immunogenicity-Score of 92.0887. The core-sequence SRLFRKSNL showed the highest Median-Percentile-Rank (7-HLA-allele) of 19. CD4+ immunogenicity also confirms the representation of the CUT4TM2 epitope SRLFRKSNL by MHC Class II. The epitope YNYKYRLFR from CUT4 showed an IC50 of ∼30 nM with allele HLA-DRB1*1101 and HLA-DRB5*0101 with plenty H-bonding. Cut4 double-mutants strongly interact with the exposed T-cell surface and are facilitated by its receptors. The MD-simulation data suggest that TM2 has a maximum RMSD value of 1.7 Å, DM2 is at 1.55 Å and SM3 is at 1.5 Å. These variations correspond to structural adjustments and involve binding/unbinding chemical interactions. The RMSD plot shows that 1KGC T-cell molecule is at 2.2 Å and the 4JRX is at 1.2 Å, which increases with the simulation time.

CONCLUSIONS:

Screening of conserved SARS-CoV-2 spike fragments helps to find the most stable antigenic-determinant which with some mutations showed better antigenicity. Further studies are necessary to develop global vaccination strategies against COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / COVID-19 / Macrophages Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / COVID-19 / Macrophages Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2022 Document Type: Article