16th International Conference on Virology, Emerging Diseases & vaccines
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Title: Spike protein of SARS-CoV-2: Impact of single amino acid mutation and effect of drug binding to the variant-insilico analysis.
Biography: Pratibha M
Novel SARS-CoV-2, a bat based virus originated in Wuhan, China caused a global pandemic in December, 2019 belongs to the Betacorona virus family. This virus mostly enters into the respiratory tract of human and enters into the cell through Angiotensin Convertase II (ACE2) receptor which is present in the epithelial layers. SARS-CoV-2 containing a single stranded RNA genome (~29Kbp) enters the cell with the help of Spike (S) protein. Spike protein is a glycoprotein responsible for receptor binding and membrane fusion. The S1 domain of spike protein has an N terminal domain (NTD) and a C-Terminal Domain (CTD). CTD is the receptor binding site. Binding is facilitated when the host cell secretes TMPRSS2 serine protease which cleaves the S1/S2 boundary of spike protein and due to this cleavage, S2 domain undergoes conformational changes and thereby it facilitates the membrane fusion of virus to host cell. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D14G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated sequences were structured and docked to ACE2 receptor using bioinformatics tool. When the mutated S protein is docked, the ∆G (free energy) value is very minimal in mutated protein and the dissociation constant (Kd) value is higher showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with more than -8.5 Kcal/mol to both wild type and mutants.