SARS-CoV-2 are enveloped RNA viruses that belong to the family Coronaviridae of genus Beta coronavirus, responsible for the COVID-19 pandemic. The mutation rate is high among RNA viruses and in particular, coronavirus replication is error prone with an estimated mutation rate of 4x10-4 nucleotide substitutions per site per year. Variants of SARS-CoV-2 have been reported from various countries like United Kingdom, South Africa, Denmark, Brazil and India. These variants evolved due to mutations in spike gene of SARS-CoV-2. The most concerning variants are Variant of Concern (VOC) 202012/01 from United Kingdom and B.1.617 variant of India. Other variants include B.1.351 lineages, cluster 5/SARS-CoV-2 variant of Denmark, 501.V2 variant/SARS-CoV-2 variant of South Africa, lineage B.1.1.248/lineage P.1 of Brazil. Mutations in S protein may result in changes in the transmissibility and virulence of SARS-CoV-2. To date, alterations in virulence or pathogenicity have been reported among the variants from many parts of the globe. In our opinion, since the S protein is significantly altered, the suitability of existing vaccine specifically targeting the S protein of SARS-CoV-2 variants is a major concern. The mutations in SARS-CoV-2 are a continuous and evolving process that may result in the transformation of naive SARS-CoV-2 into totally new subsets of antigenically different SARS-CoV-2 viruses over a period of time.