SARS CoV-2 SPIKE GLYCOPROTEIN MUTATIONS AND CHANGES IN PROTEIN STRUCTURE

Abstract

Severe Acute Respiratory Syndrome Corona Virus-2 (SARS CoV-2) is a single-stranded positive polarity RNA virus with a high virulence effect. Spike (S) glycoprotein is the outermost component of the SARS CoV-2 virion and is important in the entry of the virus into the cell via the angiotensin converting enzyme 2 (ACE2) receptor. ACE2 plays an important role in the regulation of human blood pressure by converting the vasoconstrictor angiotensin 2 to the vasodilator angiotensin 1-7. In this study, the changes that mutations in Asian isolates may cause in S glycoprotein structure were analyzed and modeled to contribute to drug and vaccine targeting studies. Genome, proteome and mutation analyses were done using bioinformatics tools (MAFFT, MegaX, PSIPRED, MolProbity, PyMoL). Protein modelling was performed using ProMod3. We detected 26 mutations in the S glycoprotein. The changes that these mutations reveal in the general topological and conformational structure of the S glycoprotein may affect the virulence features of SARS CoV-2. It was determined that mutations converted the receptor binding domain (RBD) from down-formation to like-up formation. It is thought that conformational change occurring after mutation in RBD may cause an increase in receptor affinity. These findings could be beneficial for disease prevention of and drug/vaccine development for SARS CoV-2.

Keywords

• sars cov-2
• covid19
• spike protein
• mutational changes
• protein structure