3.1 Active site analysis
Active site analysis of SARS-CoV-2 spike glycoprotein (S2), viral
nuclease (NSP15 endoribonuclease) and protease (Main Protease 3CLpro) as
conducted by DoG Site Scorer indicated that there are various active
pockets within the studied viral virulence factors with druggability
ranging from 0.12 to 0.86 (Table 1 ).
It was found that pockets P_11 (Drug score: 0.847), P_1 (Drug
score:0.860) and P_0 (Drug score: 0.805) were energetically favourable
for performing further molecular docking studies with the viral
receptors being spike glycoprotein, NSP15 endoribonuclease and Main
Protease 3CLpro, respectively. While conducting the active site
analysis, the DoG Site Scorer tool analysed the heavy atom coordinates
on the surface of the 3D structure of the respective viral receptors.
Depending on these atomic coordinates, a hypothetical grid was spanned
by outruling the chances of any spatial overlap of the grid with the
heavy atoms. Furthermore, the tool engages in applying a Gaussian filter
to the defined grids, so as to identify spherical pockets of binding.
Druggability score (0-1) of the selected spherical pockets are deduced
on the basis of their surface area, volume, enclosure and
hydrophobicity. As a general rule, higher druggability score is
indicative of a more druggable pocket (Volkamer et al., 2012). The most
druggable pockets of SARS-CoV-2 spike glycoprotein, NSP15
endoribonuclease and main protease 3CLpro have been elucidated inFig. 2 .