## 3 Results  
The cryo-electron microscopy structure of the S-Protein trimer, a subunit vaccine candidate for COVID-19 PDB: 7E/B [87], is depicted in Figure 1a, containing chain A, chain B and chain C. Chain A was separated from PDB, and the 7E/B S-Protein trimmer contains the three major units: NTD (14-305), RBD (329-521), and S2 subunit (522-1147), as described in Figure 1b. The structure of the MT-NTD and the mutation in the RBD are pictured in Figure 1c.  
The MT-NTD structure was compared with the WT-NTD, and the structural variation and coordination were evaluated. The WT-NTD (Figure 2a) and MT-NTD (Figure 2b) were validated using the Ramachandran plot. For the WT-NTD and MT-NTD, 98.92% residues were present in the most favored region, and no significant changes were noted between the WT-NTD and MT-NTD. The RMSD and sequence identity were compared for the superimposed structure of the MT-NTD with WT-NTD. The RMSD and sequence identity of the MT-NTD was 0.004 A, and 99.68%, while the WT-NTD was set as a fixed molecule. Furthermore, the stamp score was noted as 9.799 for the MT-NTD out of 10. The superimposed WT-NTD and MT-NTD structures' stamp sequence alignment is shown in Figure S1 (Supplementary File). The change in two amino acids did not produce any considerable alteration in the overall structural conformation of the protein in terms of the smaller RMSD and sequence identity. The superimposition of binding residues for the WT-NTD (Asn165, Asn234) and MT-NTD (Gln165, Gln234) models are shown in Figure 2c, respectively.  
We used 603 phytocompounds in the screening process, obtained from the 22 well-annotated herbal plants included with the Kabasura kudineer choroman (Figure 3a). After processed molecular docking, the ligands with a higher binding affinity (\(\leq\)6.0 kcal/mol) were screened from the docked results (Figure 3b).  
The effects of phytocompounds from the plants _H. cordata_, _Citrus_ spp., _N. sativa_, _O. basilicum_, _P. nigrum_, _M. speciosa Korthi_, and Kabasura kudineer, including 15 herbs, were analyzed to understand the binding efficacy against the targets N-domain and RBD domain. The docked phytocompounds with the binding affinity \(\leq\)\(-\)6.0 kcal/mol were predicted and listed separately for the MT-NTD and RBD. The phytocompounds from _H. cordata_, _S. aromaticum_, _M. speciosa Korth_, _C. serratum_, _H. auriculata_, _Andrographis paniculata_ (_A. paniculata_), _M. cerviana_, _T. involucrata_, and _T. cordifolia_ effectively inhibited the mutated N-Domain.  
Figure 1: The structure of the study protein PDB:7E7B. (**A**) The structure of SARS-CoV-2 S-protein (PDB: 7E7B) of B.1.67.2. A vaccine candidate constitutes Chain A, B, and C. (**B**) The structure of S-protein chain A contains NTD, RBD, and S2 subunit. (**C**) The structure of MT-NTD domain and RBD with its mutation as Indian delta variant B.1.617.2 S-Protein (Green—MT-NTD domain; purple—S2 subunit; yellow—RBD; the mutated residues of MT-NTD and RBD domains’ crucial residues are highlighted as Corey-Pauling–Koltun (CPK) surface structure).  
Figure 2: The B.1.617.2 S-protein wild- and mutated-type structure evaluation and comparison by implementing Ramachandran plot. (**A**) Ramachandran plot for the wild-type S-protein structure. (**B**) NTD-mutated S-protein structure (**C**) The superimposed structure of WT-NTD and MT-NTD (Green—WT-NTD; red—MT-NTD; green and blue (CPK surface)—normal and mutated residues.