journal menu
![[Figure 5]](ud5057fig5mag.jpg)
|
|
Figure 5
The workflow of the virtual screening campaign to identify inhibitors of SARS-CoV-2 NSP13. The process begins (top left) with an analysis of the myricetin binding site on NSP13. The myricetin conformer served as the foundation for the ROCS query, which was refined through interaction and sequence-conservation analyses and extended through incorporating fragments identified by Newman et al. (2021  ). The in silico assessment of the binding affinities of the myricetin moieties identified the pyrogallol moiety (green) as energetically favourable for binding to NSP13 compared with the trihydroxychromone moiety (red). These structural and computational insights guided the design of a ROCS query that combined the shapes (grey) of myricetin and the fragments while incorporating conserved chemical features such as hydrogen-bond donors (blue), acceptors (red) and aromatic rings (green). The energetically favourable features of the pyrogallol moiety were upweighted to prioritize pyrogallol-based compounds. ROCS was then employed to search for compounds matching the shape and chemical features of the query, with the results further refined through docking using HYBRID and Gnina. Promising candidates were selected based on ChemGauss4 scores, binding affinities, CNN scores, r.m.s.d. values, the presence of pyrogallol-like moieties and the availability and affordability of the compounds, which are naturally sourced. |
![[Figure 5]](ud5057fig5.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
access
