High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19

Ojha, Rupal; Gupta, Nidhi; Naik, Biswajit; Singh, Satyendra; Verma, Vijay; Prusty, Dhaneswar; Prajapati, Vijay Kumar

doi:10.1016/j.ejps.2020.105375

Cited by 49 publications

(64 citation statements)

References 46 publications

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“…The amino acid sequence corresponding to each antigenic protein was provided as input to the server individually. The epitopes were predicted by selecting default parameters for the three MHCI supertypes-A2, A3 and B7, as these three collectively cover >88% of the global population 11,22,23 .…”

Section: Identi Cation Of T C Cell Epitopesmentioning

confidence: 99%

“…Toxicity of all the generated epitopes was assessed by employing the ToxinPred server which utilizes models formulated on the technique of machine learning and quantitative matrix, by applying various peptide properties, for predicting toxicity ofthe input peptide/protein sequence 11,24 . Before combining the different non toxic epitopes for fabricating the vaccine construct, the antigenic potential of each of these predicted B, T H and T C cell epitopes were determined by using VaxiJen (version 2.0) server that is available online.…”

Section: Assessment Of Toxicity Prediction Of Antigenic Potency and mentioning

confidence: 99%

“…The different linkers utilized, have been chosen based on previous reports and are known to perform speci c functions; such as, increased proteasome processing (KK linker) 25 , improved protein exibility (GPGPG linker) 26 , site of proteasomal cleavage (AAY linker) 27 ,and promoting α helix secondary structure formations (EAAAK linker) 11 in the designed protein (vaccine molecule). The human beta defensin-3 is a well-known TLR-3 agonist, and increases the immunogenic potential of a vaccine by enhancing the effectivity of the humoral and cellular immune response; which de nes its application in the current study 28,29 .The VaxiJen server and ANTIGENpro tool of SCRATCH suite were utilized to check the e cacy of the fabricated construct.…”

Section: Assessment Of Toxicity Prediction Of Antigenic Potency and mentioning

confidence: 99%

“…Therefore, vaccine development efforts need to be accelerated using novel effective strategies. At the moment, several vaccine design efforts are underway to address this challenge, with considerable advancements in our understanding of the virus's biology 8,9,10,11 . In the past vaccine development against the outbreaks of SARS and MERS have accomplished limited success, which indicates that developing the vaccine against COVID-19 could be a formidable task to achieve 11,12 . Recently, among other approaches, the multi epitope subunit vaccine (MESV) has proved to be an e cacious approach against the virus.…”

Section: Introductionmentioning

confidence: 99%

“…Keeping this in view, we engineered the vaccine construct utilizing non-toxic antigenic epitopes against B (BCL) and T cells (HTL/T H and CTL/T C ) by utilizing non-structural proteins viz. non-structural protein 2 (NSP2), non-structural protein 8 (NSP8), and helicase, which are referred as the tool proteins executing the viral replication 11 and structural proteins, namely nucleoprotein (N) and receptor binding domain (RBD) of the spike (S) protein. NSP2 is known to be conserved in both SARS-CoV and SARS-CoV-2;it bindsto two host proteins, namely prohibitin 1 and prohibitin 2 which are vital for cell cycle passage, cellular differentiation, apoptosis, cell migration and mitochondrial biogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Engineering a Multi Epitope Vaccine Against SARS-CoV-2 By Exploiting Its Non Structural and Structural Proteins

Rajput

Sharma

Kumari

et al. 2020

Preprint

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Abstract SARS-CoV-2, the causative agent behind the ongoing pandemic exhibits an enhanced potential for infection when compared to its related family members- the SARS-CoV and MERS-CoV; which have caused similar disease outbreaks in the past. The severity of the global health burden, increasing mortality rate and the emergent economic crisis urgently demands the development of next- generation vaccines. Amongst such emergent next generation vaccines are the multi-epitope subunit vaccines, which hold promise in combating deadly pathogens. In this study we have exploited immunoinformatics applications to delineate a vaccine candidate possessing multiple B and T cells epitopes utilizing the SARS-CoV-2 non structural and structural proteins. The antigenicity potential, safety, structural stability and the production feasibility of the designed construct was evaluated computationally. Furthermore, due to the known crucial interactions of human TLR-3 immune receptor with SARS-CoV, the vaccine construct was examined for its binding efficiency using molecular docking and molecular dynamics simulation studies, which resulted in strong and stable interactions. Finally, the immune simulation studies suggested an effective immune response on vaccine administration. Overall, the immunoinformatics analysis advocates that the purposed vaccine candidate is safe and immunogenic and therefore can be pushed as a lead for in vitro and in vivo investigations.

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Section: Identi Cation Of T C Cell Epitopesmentioning

confidence: 99%

Section: Assessment Of Toxicity Prediction Of Antigenic Potency and mentioning

confidence: 99%

Section: Assessment Of Toxicity Prediction Of Antigenic Potency and mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Engineering a Multi Epitope Vaccine Against SARS-CoV-2 By Exploiting Its Non Structural and Structural Proteins

Rajput

Sharma

Kumari

et al. 2020

Preprint

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Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

Ojha

Prajapati

2021

Journal Cellular Physiology

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Vaccination is a significant advancement or preventative strategy for controlling the spread of various severe infectious and noninfectious diseases. The purpose of vaccination is to stimulate or activate the immune system by injecting antigens, i.e., either whole microorganisms or using the pathogen's antigenic part or macromolecules. Over time, researchers have made tremendous efforts to reduce vaccine side effects or failure by developing different strategies combining with immunoinformatic and molecular biology. These newly designed vaccines are composed of single or several antigenic molecules derived from a pathogenic organism. Although, whole‐cell vaccines are still in use against various diseases but due to their ineffectiveness, other vaccines like DNA‐based, RNA‐based, and protein‐based vaccines, with the addition of immunostimulatory agents, are in the limelight. Despite this, many researchers escape the most common fundamental phenomenon of protein posttranslational modifications during the development of vaccines, which regulates protein functional behavior, evokes immunogenicity and stability, etc. The negligence about post translational modification (PTM) during vaccine development may affect the vaccine's efficacy and immune responses. Therefore, it becomes imperative to consider these modifications of macromolecules before finalizing the antigenic vaccine construct. Here, we have discussed different types of posttranslational/transcriptional modifications that are usually considered during vaccine construct designing: Glycosylation, Acetylation, Sulfation, Methylation, Amidation, SUMOylation, Ubiquitylation, Lipidation, Formylation, and Phosphorylation. Based on the available research information, we firmly believe that considering these modifications will generate a potential and highly immunogenic antigenic molecule against communicable and noncommunicable diseases compared to the unmodified macromolecules.

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COVID‐19 drug repurposing: A review of computational screening methods, clinical trials, and protein interaction assays

Wang

Guan

2020

Medicinal Research Reviews

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The situation of coronavirus disease 2019 (COVID‐19) pandemic is rapidly evolving, and medical researchers around the globe are dedicated to finding cures for the disease. Drug repurposing, as an efficient way for drug development, has received a lot of attention. However, the huge amount of studies makes it challenging to keep up to date with the literature on COVID‐19 therapeutic development. This review addresses this challenge by grouping the COVID‐19 drug repurposing research into three large groups, including clinical trials, computational research, and in vitro protein‐binding experiments. Particularly, to facilitate future drug discovery and the creation of effective drug combinations, drugs are organized by their mechanisms of action and reviewed by their efficacy measured by clinical trials. Providing this subtyping information, we hope this review would serve the scientists, clinicians, and the pharmaceutical industry who are looking at the new therapeutics for COVID‐19 treatment.

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High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19

Cited by 49 publications

References 46 publications

Engineering a Multi Epitope Vaccine Against SARS-CoV-2 By Exploiting Its Non Structural and Structural Proteins

Engineering a Multi Epitope Vaccine Against SARS-CoV-2 By Exploiting Its Non Structural and Structural Proteins

Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

COVID‐19 drug repurposing: A review of computational screening methods, clinical trials, and protein interaction assays

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