The COVID-19 pandemic is still raging around the world, with around 210 million confirmed cases and more than 4.4 million deaths across almost all countries. SARS-CoV-2 virus is highly transmissible and pathogenic coronavirus, causing the disease. A large number of SARS-CoV-2 variants have been reported worldwide. Among them, 4 variants of concern include Alpha, Beta, Gamma, and Delta. Currently, the original virus strain was largely replaced by Delta variant which became predominant. In this review, we highlight the SARS-CoV-2 virus and a few variants, focusing on their genomic structures and viral proteins encoded. We also discussed their more fatality, rising transmissibility along with a drop of vaccine activity against causative agent. We further explained the possible reasons for the change from the structural points of view. This may help with developing better drugs and vaccines for preventing the pandemic and treatment of the disease.