Immunoinformatics approaches towards developing vaccine/therapeutic agent against the Middle East Respiratory Syndrome Coronavirus by targeting nsp3 protein

Abstract

MERS coronavirus is an emerging virus which causes Middle East respiratory syndrome. MERS outbreak has been appearing in 27 different countries over a span of around six years with a mortality rate greater than 35% and claimed over 800 lives in the process. However, there is not any clinically approved vaccine or therapeutic agent available for treatment of MERS. Therefore, it is crucial to design an effective vaccine or therapeutic agents against MERS coronavirus. This study aimed to find vaccines/therapeutic agents against MERS coronavirus using immunoinformatics which could reduce both time and cost needed for laboratory analysis and vaccine development. Since nsp3 protein is an essential component of the replication/transcription complex of MERS coronavirus, the discovery of an nsp3 inhibitor will be a major leap towards developing an anti-viral agent that can interfere with MERS coronavirus replication. In the present study, two different strategies were explored. The first strategy was to design an epitope-based vaccine. For designing an epitope-based vaccine, nsp3 protein sequence was extracted from the NCBI database and then the sequence was put in T-cell and B-cell epitope prediction servers to generate a list of potential T-cell and B-cell epitope candidates. T-cell and B-cell epitope candidates are then screened using several software and tools. FAFETGLAY appeared to be the best T-cell epitope candidate. However, the only drawback was that FAFETGLAY was found as an allergen in allergenicity prediction tools. FVDWRSYNYAVSSAFWLF, LKFKEVCKTTTGIPEY and LKFKEVCKTTTGIPEYNF showed promise as epitope candidates for peptide-based vaccine design among the selected B-cell epitopes. The second strategy was focused on identifying effective flavonoids that can be used as nsp3 inhibiting therapeutic agents against MERS coronavirus. In this study, 18 flavonoids were selected as potential nsp3 inhibitor candidates and their anti-viral activities were assessed using molecular docking study. Molecular docking study revealed that among 18 flavonoids, apiin and naringin exhibited the most potent antiviral activity against MERS coronavirus nsp3 protein as they showed the best binding affinity of -10.1 kcal/mol which was higher than the binding affinity of ADP-ribose. In addition, apiin and naringin had the lowest Ki value of 0.0390649 μM. Furthermore, the molecular visualization of the docked complexes suggested that both apiin and naringin formed three or more hydrogen bonds ranging from moderate to weak. Therefore, apiin and naringin can be considered good candidates for further evaluation as potential anti-viral agents against MERS-CoV.