Designing of Nucleocapsid Protein Based Novel Multi-epitope Vaccine Against SARS-COV-2 Using Immunoinformatics Approach

Kumar, Janish; Qureshi, Rahila; Sagurthi, Someswar Rao; Qureshi, Insaf Ahmed

doi:10.1007/s10989-020-10140-5

Cited by 23 publications

(17 citation statements)

References 37 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N is a multifunctional protein required for efficient genome replication ( 10 ) and transcription of CoV ( 11 ) in addition to its involvement in viral assembly ( 12 ). The N protein is also conserved ( 13 ), stable, and highly immunogenic ( 14 , 15 ) and has therefore been proposed as one of the major targets for the development of SARS-CoV-2 therapeutics and vaccines ( 15 – 17 ). Nsp15, a nidoviral RNA uridylate-specific endoribonuclease (NendoU), is present in all coronaviruses ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies

Nguyen

Falzarano

Gerdts

et al. 2021

J Virol

View full text Add to dashboard Cite

The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide resulting in global public health emergencies and economic crises. In this study, a non-infectious and biocontainment level-2 compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high-throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting non-structural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, an FDA-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof-of-principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL-2 compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In this study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level (BSL) 3 facility, the replicon is non-infectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology.

show abstract

Section: Introductionmentioning

confidence: 99%

Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies

Nguyen

Falzarano

Gerdts

et al. 2021

J Virol

View full text Add to dashboard Cite

show abstract

“…Finally, in SARS-CoV-2 vaccine development, an adjuvant stimulating the evolutionary-conserved, IRAK4-IRF5 pathway should be an ideal partner for a SARS-CoV-2 vaccine. IRAK4-IRF5 pathway activators could be included in multi-epitope vaccines (149). Such formulations should promote optimum immune responses and immunological memory (150).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Stoy

2021

Front. Immunol.

View full text Add to dashboard Cite

Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.

show abstract

“…WATER TOOL software was used to achieve pairwise sequence alignment. 6JKZ and 6KMF were screened for average antigenic propensity and allergenicity using the antigenic peptides prediction tool ( http://imed.med.ucm.es/Tools/antigenic.pl ) and the AllerTop v2.0 servers ( http://ddg-pharmfac.net/AllergenFP/ ) ( Kumar et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Default settings of weight on C-terminal cleavage and TAP transport efficiency were maintained. Class I Immunogenicity of the IEDB server ( http://tools.iedb.org/immunogenicity/ ) and VaxiJen v2.0 ( http://www.ddgpharmfac.net/vaxijen/VaxiJen/VaxiJen.html ) were successively used to determine immunogenicity and antigenicity respectively ( Kumar et al, 2021 ). The MHC-I binding alleles of selected CTL epitopes were identified using the MHC-I binding predictions of the IEDB server ( http://tools.iedb.org/mhci/ ) using a conventional technique with a percentile rank of <2.…”

Section: Methodsmentioning

confidence: 99%

“…The vaccine candidate contains T - helper (HTL), cytotoxic T-lymphocyte (CTL), and B-cell lymphocyte (BCL) epitopes which are critical for antibody generation. Molecular docking was used to validate the vaccine candidate's association, binding mechanism, and reliability with the human host's immune receptor CXCR4 to develop an innovative and potentially multi-epitope vaccine that could pave the way for a peri -implantitis vaccine ( Kumar et al, 2021 ). We prioritised a group of epitopes using a computer-aided technique based on sequence conservation criteria and biological properties of their antigens of origin.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Designing an immunoinformatic vaccine for peri-implantitis using a structural biology approach

Yadalam

Rengaraj

Mugri

et al. 2022

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Objectives Peri-implantitis is a destructive inflammatory process that affects the soft and hard tissues around dental implants. porphyromonas gingivalis , an anaerobic gram-negative bacterium, appears to be the main culprit. Since there is no efficient and specific vaccine to treat peri -implantitis, the goal of our research has been to develop a multi-epitope vaccination utilizing an immunoinformatics approach that targeted P. gingivalis type I fim A. Materials and methods P. gingivalis peptides 6JKZ and 6KMF are suitable for vaccine development. B- and T-cell epitopes from 6KMF and 6JKZ were detected and evaluated based on critical factors to produce a multi-epitope vaccine construct. It was assessed based on allergenicity, antigenicity, stability. The vaccine's dual major histocompatibility complex (MHC-I and MHC-II) binding epitopes allowed it to reach a larger population. P. gingivalis fimbriae induce immune subversion through TLR -CXCR4 receptor complex pathway. The ClusPro 2.0 server was used to do the molecular docking using TLR2 - CXCR4 and vaccine epitopes as receptor and ligand respectively. Results The designed vaccine was non-allergenic and had a high antigenicity, solubility, and stability. The 3D structure of the vaccine revealed strong interaction with CXCR4(TLR2) using molecular docking. The vaccine-CXCR4 interface was more consistent, possibly because the vaccination has a higher affinity for the CXCR4-TLR2 complex. Conclusion This study details the vaccine's distinct and sustained interaction with the CXCR4(TLR2) immunological receptor and its consistent and effective utterance in the bacterial system. As a result, our vaccine formulation will evoke a significant memory response and induce an adaptive immune response against P. gingivalis .

show abstract

Designing of Nucleocapsid Protein Based Novel Multi-epitope Vaccine Against SARS-COV-2 Using Immunoinformatics Approach

Cited by 23 publications

References 37 publications

Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies

Construction of a Noninfectious SARS-CoV-2 Replicon for Antiviral-Drug Testing and Gene Function Studies

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Designing an immunoinformatic vaccine for peri-implantitis using a structural biology approach

Contact Info

Product

Resources

About