SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus) poses an unprecedented public health threat to the mankind globally since December 2019. Considering the escalating number of positive cases, the World Health Organization announced public health crisis on 11^th March 2020 worldwide. The pathogenesis of SARS-CoV-2 (causal agent of COVID-19) is not clearly understood till date and the role of antiviral therapeutics is yet to be established for this pandemic. The objective of our study was to compare the SARS-CoV-2 sequence of Wuhan virus with those of Indian SARS-CoV-2 isolates; only those mutations which occurred in the helicase (nsp13) region were addressed and used for subsequent study. For mutational characterization multiple sequence alignment was done followed by protein dynamics study using Chimera and Dynamut software. Altogether, 51 mutations were detected in the nsp13 of Indian SARS-CoV-2, out of them 7 mutants were used for subsequent study. Furthermore, prediction of secondary structure as well as protein dynamics study revealed that these mutations altered the structural stability and flexibility of helicase protein. In this in silico study, predictive tools of immunoinformatic were used for the prediction of B-cell, T-cell and MHCI epitopes. Two mutations have been detected in the predicted epitope region of SARS-CoV-2 helicase that might induce its conformational changes and considered as a major challenge in the development of vaccine. The present investigation was, therefore, undertaken to analyze one of the crucial drug target like helicase which is indispensable for the replication /transcription machinery of SARS-CoV-2.