## 4 Discussion  
The altered viral subset will become predominant in the context of environmental switches. In the face of such problems in treatment planning, there is now strong necessity for alternative therapy. Natural substances, which have been used globally for many years due to their chemical variety, species diversity, and drug-like features, may be recognized in this category. In this line, we aimed to assess the anti-COVID-19 capability of Siddha polyhedral formulation and plant extracts containing different phytocompounds that have been previously reported to have antiviral properties [54,55]. The SARS-spike CoV-2 protein has undergone mutations and is heavily glycosylated; hence, the biological relevance of viral alterations must be investigated promptly [40,131]. [PERSON] et al. examined over 80 variations and 26 glycosylation site variations to identify the severity of disease transmission and sensitivity from recovered patients. The mutated residue N234Q was significantly resistant to neutralizing antibodies, whereas N165Q became more susceptible [48]. Similarly, the Indian delta variant B.1.617.2. carries five particular mutations: L452R, T478K, E484Q, D614G, and P681R [12,20,132]. It controls viral fitness by increasing the ACE2 receptor binding affinity, increasing infectivity, and deactivating the antibodies. These mutations in the Indian delta variant increased the spike's stability, viral infectivity, and stronger cell attachment, thereby promoting viral replication, transmissibility, and pathogenicity [12,29,133,134]. These discoveries could help with vaccine and therapeutic antibody development [40]. Drugs derived from medicinal plants have traditionally been widely utilized to treat diseases [135, 136, 137, 138]. However, effective medication is strongly advocated at this key stage of COVID-19 and its variant infection [1]. Plants are rich in phytocompounds, which could efficiently counteract with COVID-19 [139,140]. Hence, the MT-NTD and RBD domains in the SARS-CoV-2 were docked using 603 phytochemicals in this investigation. Many of the phytocompounds found in plants had high protein-binding abilities. After applying the threshold criteria of \(\leq\)\(-\)6.0 kcal/mol to 603 compounds, 27 and 13 phytocompounds for the MT-NTD and RBD, respectively, were screened. Phytocompounds with a binding affinity of \(\leq\)\(-\)6.0 kcal/mol were chosen because they showed promising inhibition with crucial residues N234Q, N165Q, L452R, T478K, and E484Q against the MT-NTD and RBD. Typically, the threshold is chosen by correlating it to known inhibitors that have been previously published and biologically verified. In this regard, we selected ceftaxone, a standard drug that evidenced higher binding affinity toward both the NTD and RBD than the FDA-approved anti-viral drugs lopinavir [141],  
Figure 5: The docking pose of the RBD with the most promising phytocompounds based on the binding affinity and interacting residues (**A**,**D**,**G**,**J**). The docking poses with ceftaxone, kanzonol V, progeldanamycin and rhodoxanthin (**B**,**E**,**H**,**K**). The hydrophobicity of the interacting residues (brown (\(\uparrow\) hydrophobicity)-blue (\(\downarrow\) hydrophobicity), (**C**,**F**,**I**,**L**). The type of bonds involved in interacting phytocompounds with RBD residues (**M**–**P**). The LigPlot interaction for the phytocompounds docked with RBD residues. remdesivir [142], chloroformquine [143], umifenovir [144], favipiravir [145], ribavirin [146], hydroxychloroquine [147], sofosbuvir [148], and oseltamivir [4]. However, ceftaxone shows less binding affinity at \(-6.3\) kcal/mol and \(-6.5\) kcal/mol towards the MT-NTD and RBD domains. Likewise, there is no interaction with the specified residues accounting for the targeted MT-NTD and RBD of the S-Protein of the Indian delta variant B.1.617.2. The root of _C. serratum_ is reported to treat respiratory disease, fever, inflammation, cancer, nociceptive, liver disorders, and allergic condition, as well as to act as an antioxidant [63, 64, 116, 117].