Fig 1.
TPMS-ANN approach has been used to identify drugs for repurposing against set 1. The potential MoA of drugs repurposed for sets 1, 2 and 3 have been identified by TPMS and GUILDify approaches.
Fig 2.
Key interactors in the predicted mechanism of action of pirfenidone and melatonin combination therapy targeting the coronavirus-host interaction set.
Fig 3.
Network of the SARS-CoV-2 entry points and the shared interactions with pirfenidone and melatonin.
The extended set of proteins associated with the SARS-CoV-2 entry points, pirfenidone and melatonin were obtained with GUILDify v2.0. In the network, seeds are represented as octagons, non-seeds as circles and “linkers” as diamonds. “Linkers” are non-top-scoring proteins (they do not belong to any of the represented sets) that link unconnected groups of proteins to the largest connected component. “Linkers” are represented in this plot to facilitate the visualization, but they are not associated to any of the sets of proteins, thus having a less relevant role in the interpretation of the results. Pirfenidone-associated proteins are coloured in orange, melatonin-associated proteins are coloured in green and proteins associated with both drugs in brown.
Fig 4.
Proteins associated to ARD set modulated by pirfenidone and melatonin individually and in combination.
The MoA has been calculated for each drug individually and in combination for each of the subsets defining ADR set. The first 3 columns provide the % and absolute value of affected proteins in the set for each MoA. Last column provides the cumulative, showing the protein overlaps affected between the different treatments.
Fig 5.
Key interactors in the predicted mechanism of action of pirfenidone and melatonin combination over the ARD set.
Only the most relevant ARD effectors appear in the figure, represented as octagons.