COVID-19 treatment: Combining anti-inflammatory and antiviral therapeutics using a network-based approach

Network-based rational design of effective drug combinations for COVID-19. (A) Four possible exposure modes of the COVID-19 disease module to the targets of pairwise drug combinations. An effective drug combination can be captured by the complementary exposure pattern in which the targets of the drugs both hit the COVID-19 disease module (molecular determinants of disease pathophysiology in the human interactome) but target separate neighborhoods in the human protein-protein interactome network. In model, Z_CA and Z_CB denote the network proximity (Z-score) between drug targets (drugs A and B) and COVID-19 disease module. S_AB denotes the separation score of drug targets. (B and C) The complementary exposure pattern of melatonin (a hormone synthesized in the pineal gland) plus toremifene (a selective estrogen receptor modulator) on the COVID-19 disease module, as described in our network medicine methodologies.^10,23 For a network-based approach to COVID-19 drug combinations to be effective, we need to establish whether the topological relationship between two drug-target modules reflects biological and pharmacological relationships while also quantifying their network-based relationship to COVID-19 disease modules in the human protein-protein interactome.¹⁰