Designing spike protein (S-Protein) based multi-epitope peptide vaccine against SARS COVID-19 by immunoinformatics

Abstract Background Recently the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated a significant need on identifying drugs or vaccines to prevent or reduce clinical infection of Coronavirus disease – 2019 (COVID-19). In this study, immuno-informatics tools were utilized to design a potential multi-epitopes vaccine against SARS-CoV-2 spike S protein. Structural analysis for SARS-CoV-2 spike S protein was also conducted. Method: SARS-CoV-2 spike S protein sequences were retrieved from the GeneBank of National Central Biotechnology Information (NCBI). Immune Epitope Database (IEDB) tools were used to predict B and T cell epitopes, to evaluate their allergenicity, toxicity and cross- reactivity and to calculate population coverage. Protparm sever was applied to determine protein characterization of spike protein and predicted epitopes. Molecular docking for the proposed MHCI epitopes were also achieved against Tall like Receptor (TLR8) receptors and HLA-B7 allele. Result Immuno-informatics analysis of S protein using IEDB identified only one B cell epitope 1054QSAPH1058 as linear, surface and antigenic. Although 1054QSAPH1058 was estimated as non-allergic and non-toxic, it showed protein instability. Moreover, around 45 discontinuous epitopes were also recognized as different exposed surface area. In MHCI methods, six conserved stable and safe epitopes (898FAMQMAYRF906, 258WTAGAAAYY266 and 2FVFLVLLPL10, 202 KIYSKHTPI210, 712IAIPTNFTI720 and 1060VVFLHVTYV1068) were identified. These epitopes showed strong interaction when docked with TLR8 and HLA-B7 allele especially 1060VVFLHVTYV1068 and 2FVFLVLLPL10 epitopes. Three epitopes were also predicted (898FAMQMAYRF906, 888FGAGAALQI896 and 342FNATRFASV350) using MHCII methods. Furthermore, the potential multi-epitopes were acquired by assessing allergenicity, toxicity and cross-reactivity to prevent autoimmunity. Conclusion The multi-epitopes vaccine was predicted based on Bioinformatics tools that may provide reliable results in a shorter time and at a lower cost. However, further in vivo and in vitro studies are required to validate their effectiveness.

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Vaccine Design against Coronavirus Spike (S) Glycoprotein in Chicken: Immunoinformatic and Computational Approaches

10.21203/rs.3.rs-25375/v2 ◽

2020 ◽

Author(s):

Eman Ali Awadelkareem ◽

Sumaia Awad Elkariem Ali

Keyword(s):

T Cell ◽

Rna Virus ◽

Protein S ◽

Economic Loss ◽

Protein Characterization ◽

Spike Protein ◽

T Cell Epitopes ◽

Resistance Response ◽

S Protein ◽

Infectious Bronchitis

Abstract Background: Infectious bronchitis (IB) is a highly contagious respiratory disease in chickens and produces economic loss within the poultry industry. This disease is caused by a single stranded RNA virus belonging to Cronaviridae family. This study aimed to design a potential multi-epitopes vaccine against Infectious bronchitis virus spike protein (S). Protein characterization was also performed for IBV spike protein.Methods: The present study used various tools in Immune Epitope Database (IEDB) to predict conserved B and T cell epitopes against IBV spike (S) protein that may perform a significant role in provoking the resistance response to IBV infection. Results: In B cell prediction methods, three epitopes (1139KKSSYY1144, 1140KSSYYT1145, 1141SSYYT1145) were selected as surface, linear and antigenic epitopes. Many MHCI and MHCII epitopes were predicted for IBV S protein. Among them 982YYITARDMY990 and 983YITARDMYM991 epitopes displayed high antigenicity, no allergenicity and no toxicity as well as great linkage with MHCI and MHCII alleles. Moreover, docking analysis of MHCI epitope produced strong binding affinity with BF2 alleles. Conclusion: Five conserved epitopes were expected from spike glycoprotein of IBV as the best B and T cell epitopes due to high antigenicity, no allergenicity and no toxicity. In addition, MHC epitopes showed great linkage with MHC alleles as well as strong interaction with BF2 alleles. These epitopes should be designed and incorporated and then tested as multi-epitope vaccine against IBV.

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Immuno-informatics Design of a Multimeric Epitope Peptide Based Vaccine Targeting SARS-CoV-2 Spike Glycoprotein

10.1101/2020.07.30.228221 ◽

2020 ◽

Author(s):

Onyeka S. Chukwudozie ◽

Clive M. Gray ◽

Tawakalt A. Fagbayi ◽

Rebecca C. Chukwuanukwu ◽

Victor O. Oyebanji ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Peptide Vaccine ◽

Spike Protein ◽

Cell Mediated Immunity ◽

Epitope Peptide ◽

Mhc I ◽

B Cell Epitopes ◽

Antibody Recognition

ABSTRACTDeveloping an efficacious vaccine to SARS-CoV-2 infection is critical to stem COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in the design of an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers along with 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC-I and II alleles respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. The vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, with triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We therefore propose that potential vaccine designs consider this approach.

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Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

10.26434/chemrxiv.11871402.v3 ◽

2020 ◽

Cited By ~ 13

Author(s):

Micholas Smith ◽

Jeremy C. Smith

Keyword(s):

Small Molecules ◽

High Throughput Screening ◽

Protein S ◽

Host Cells ◽

Spike Protein ◽

The Novel ◽

S Protein ◽

Host Virus Interactions ◽

Virus Interactions ◽

Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.

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SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

10.1101/2021.01.14.426695 ◽

2021 ◽

Author(s):

George W. Carnell ◽

Katarzyna A. Ciazynska ◽

David A. Wells ◽

Xiaoli Xiong ◽

Ernest T. Aguinam ◽

...

Keyword(s):

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Protein S ◽

Spike Protein ◽

Receptor Binding Site ◽

S Protein ◽

Closed State ◽

S Proteins ◽

Protein Constructs

AbstractThe majority of SARS-CoV-2 vaccines in use or in advanced clinical development are based on the viral spike protein (S) as their immunogen. S is present on virions as pre-fusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described that act against both open and closed conformations. The long-term success of vaccination strategies will depend upon inducing antibodies that provide long-lasting broad immunity against evolving, circulating SARS-CoV-2 strains, while avoiding the risk of antibody dependent enhancement as observed with other Coronavirus vaccines. Here we have assessed the results of immunization in a mouse model using an S protein trimer that is arrested in the closed state to prevent exposure of the receptor binding site and therefore interaction with the receptor. We compared this with a range of other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induce a long-lived, strongly neutralizing antibody response as well as T-cell responses. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralising responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, virus-inhibiting immune responses than open spikes, and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. Together with their improved stability and storage properties we suggest that closed spikes may be a valuable component of refined, next-generation vaccines.

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Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus

10.1101/2020.07.08.193672 ◽

2020 ◽

Cited By ~ 1

Author(s):

Federico Cocozza ◽

Ester Piovesana ◽

Nathalie Névo ◽

Xavier Lahaye ◽

Julian Buchrieser ◽

...

Keyword(s):

Membrane Fusion ◽

Extracellular Vesicles ◽

Protein S ◽

Spike Protein ◽

S Protein ◽

Surface Receptor

ABSTRACTSARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is 500 to 1500 times more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.

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Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface

10.26434/chemrxiv.11871402.v4 ◽

2020 ◽

Cited By ~ 26

Author(s):

Micholas Smith ◽

Jeremy C. Smith

Keyword(s):

Small Molecules ◽

High Throughput Screening ◽

Protein S ◽

Host Cells ◽

Spike Protein ◽

The Novel ◽

S Protein ◽

Host Virus Interactions ◽

Virus Interactions ◽

Ranked List

The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.

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Identification of a Potent Inhibitor Targeting the Spike Protein of Pandemic Human Coronavirus, SARS-CoV-2 by Computational Methods

10.26434/chemrxiv.12197934.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

SRUTHI UNNI ◽

Snehal Aouti ◽

Padmanabhan Balasundaram

Keyword(s):

Vaccine Development ◽

Protein S ◽

Dynamics Simulation ◽

Spike Protein ◽

Simulation Studies ◽

Viral Pathogen ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Chemical Libraries ◽

Pi Interactions

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for an outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In-silico screening, docking and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein – ACE2 interface by making substantial pi-pi interactions with Tyr505 in the ‘Site 1’ hook region of RBD and hydrophilic interactions with Glu406, Ser494 and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a potent repurpose drug to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host.

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Identification of a Potent Inhibitor Targeting the Spike Protein of Pandemic Human Coronavirus, SARS-CoV-2 by Computational Methods

10.26434/chemrxiv.12197934 ◽

2020 ◽

Author(s):

SRUTHI UNNI ◽

Snehal Aouti ◽

Padmanabhan Balasundaram

Keyword(s):

Vaccine Development ◽

Protein S ◽

Dynamics Simulation ◽

Spike Protein ◽

Simulation Studies ◽

Viral Pathogen ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Chemical Libraries ◽

Pi Interactions

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for an outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In-silico screening, docking and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein – ACE2 interface by making substantial pi-pi interactions with Tyr505 in the ‘Site 1’ hook region of RBD and hydrophilic interactions with Glu406, Ser494 and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a potent repurpose drug to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host.

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An Impedimetric Approach for COVID-19 Detection

The Analyst ◽

10.1039/d1an01718g ◽

2021 ◽

Author(s):

Yudum Tepeli ◽

Burak Ekrem Citil ◽

U. Anik

Keyword(s):

Protein S ◽

Spike Protein ◽

S Protein ◽

Infection Mechanism ◽

Biosensor System ◽

Electrochemical Approach

In this study, an electrochemical approach for the determination of coronavirus disease (COVID-19) was developed. The biosensor system relied on the spike protein (S-protein) based infection mechanism of the virus...

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