SARS-CoV 2 spike protein S1 subunit as an ideal target for stable vaccines: A bioinformatic study

S.N., Nagesha; B.N., Ramesh; C., Pradeep; K.S., Shashidhara; Ramakrishnappa, Thippeswamy; B.T., Krishnaprasad; S.M., Jnanashree; M., Manohar; N., Arunkumar; Yallappa; D., Dhanush Patel; T.V., Rakesh; E., Girish; Bagoji, Mahantesh; Chandaragi, Shreeram S.

The Covid-19 a pandemic infectious disease and affected life across the world resulting in over 188.65 million confirmed cases across 223 countries, territories and areas with 4.06 million deaths. It is caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2), while the S2 subunit mediates viral cell membrane fusion. Hence, it is a key target for developing neutralizing antibodies. Here, we have performed phylogenetic analysis and structural modeling of the SARS-CoV-2 spike glycoprotein, which is found highly conserved. The overall percent protein sequence identity from the SARS-CoV-2 spike protein sequences from the NCBI database was 99.68%. The functional domains of the S protein reveal that the S1 subunit was highly conserved (99.70%) than the S2 subunit (99.66%). Further, the 319–541 residues (RBD) of amino acids within the S1 domain were 100% similar among the spike protein. The 3D modeling of SARS-CoV-2 spike glycoprotein indicated that S protein has four domains with five protein units and the S1 subunit from 1 to 289 amino acid of domain 1 is highly conserved without any change in the ligand interaction site. This analysis clearly suggests that the S1 subunit (RBD 319–541) can be used as a target region for stable and safe vaccine development.