Rational design of multi epitope-based subunit vaccine by exploring MERS-COV proteome: Reverse vaccinology and molecular docking approach

Abstract

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

Investigate Inhibitory Effects of Ginger polyphenols compare to Simvastatin towards HMG-CoA reductase: An Integrated Molecular Docking and Molecular dynamic simulation

“…The root mean square fluctuation (RMSF) for all atoms of the HMG-CoA reductase-ginger extracts complex shows fluctuations within 0.1–1.2nm. In line with previous studies RMSF is an important parameter that yields data about the structural adaptability of Cα atoms of every residue in the system [29 30 31 35] . RMSF shows the fluctuation of terminal amino acids between 250-446aa, which is consistence with previous study [15] .…”

“…But, few study reported a comparison of simvastatin efficacy with ginger rhizome extract to show similarity and difference amongst the two to manage dyslipidemia. At the present time, several studies have been revealed the significant out of using computational approaches to investigate small molecules-target interactions [29 30 31 32 33] . In this study, we applied molecular docking, molecular dynamics (MD) simulations, and other computer aided drug design (CADD) methods to study HMG-CoA reductase and ginger extract.…”

“…Inhibitors of this enzyme are useful in managing dyslipidemia and in prevention of macrovascular and microvascular complication. In present days, computational techniques offer convenient approach for analysis of possible inhibitor of target molecules in the area medical science [27 28 29 30 31 32 33] . Here, ADMET, Auto-Dock and molecular dynamics (MD) simulations approaches have been utilized by using HMG-CoA reductase as target.…”

A Rationally Designed Bovine IgA Fc Scaffold Enhances in planta Accumulation of a VHH-Fc Fusion Without Compromising Binding to Enterohemorrhagic E. coli

“…Regarding the appropriateness of using a predicted structure for rational design, a previous validation study of I-TASSER on de novo protein design of 87 proteins showed that I-TASSER could accurately fold the designed sequences with an average root mean square deviation (RMSD) of 2.1Å (Mitra et al, 2013). Previous studies have also used I-TASSER for rationally designing stability into a variety of proteins (Wan et al, 2019;Guo et al, 2019;Ashfaq et al, 2021). Still, the resolution of the model is a key limitation on the success rate of the designed screen whereby inaccurately estimated surface exposure of asparagine and glutamine residues or the Cα distance of neighboring cysteines directly affects the prediction of supercharging or de novo disulfide mutations respectively.…”

Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design

“…Currently, several strategies for developing and designing competent and effective next-generation multi-epitope vaccines based on immunoinformatics approaches are readily available [70]. Previously, immunoinformaticsbased approaches have been employed to propose efficient multi epitope vaccine candidates for Lassa virus [71], Zika Virus [46], Dengue virus [72], influenza virus [73], Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) virus [74,75], Respiratory Syncytial Virus [76], Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) [77][78][79], chikungunya virus (CHIKV) [80] and many others. Because of the enormously reported merits and wide acceptability we adopted immunoinformatics-based approaches to de-sign an effective vaccine candidate against Pakistani-based HCV subtype-3a that could efficiently enhance immune response after vaccination.…”