Investigation of the current mutations in SARS-COV-2 variants and how they affect the spike glycoprotein structure

Abstract

SARS-COV-2 is the virus the causes COVID-19; a disease which has caused a global pandemic from 2020 till date. The COVID-19 pandemic has lasted for more than two years and has claimed more than 5 million lives globally, 234,192 lives in Africa and 3,394 deaths in Uganda as of January 2022. The reason for its long duration and persistence is the development of many variants of the virus which have various mutations. These mutations occur easily within the virus due to the absence of a proof reading mechanism by the replicase-transcriptase enzyme which is responsible replicating the genome of this virus. SARS-COV-2 has a Spike protein which is complexed with some sugars, therefore it is sometimes referred to as Spike glycoprotein. The spike protein is enables entry of the virus into the host cells via the ACE 2 receptor. Since the Spike protein has such a vital role, it was necessary to study the mutations that occur within it to find out how they affect its function. This study was computer based, involving the retrieval of protein sequences from NCBI database. These sequences were manipulated using online software such as; MEGA-X software for MSA and phylogenesis, SIFT and provean to predict the effect of the mutations on the protein function, SWISS-MODEL and I-TASSER for homology modeling and PyMOL for visualization of the protein models. The analysis of the protein models was done using Ramachandran plots and their Z-scores. In this study, it was found out the most of the mutations in the Spike protein of the selected SARS-COV-2 variants have tolerant effects i.e. do not change the Spike protein function. Though showing tolerant effects, these mutations may increase or decrease the infectivity of virus and resistance to host immune response.