Network Pharmacology analysis of orally bioavailable SARS-COV2 protease inhibitor shows synergistic targets to improve clinical efficacy

Abstract

Introduction: Orally bioavailable SARS-CoV2 antiviral drugs will significantly improve the clinical management of the disease. PF07321332 (PF32) one such orally bioavailable SARS-CoV2 protease inhibitor which can be helpful to prevent viral replication in the host. Material and methods: Hence this study evaluated the network pharmacology of PF32 using established methods to predict its potential safety and efficacy. Results: PF32 was selective against SARS-CoV2 proteases without any affinity against SARS-CoV2 RNA polymerase or its spike protein. While PF32 showed pharmacologically relevant affinity against several targets in human tissues. The target profiling of PF32 indicated a fourfold selectivity towards several proteases in human tissues with an affinity (IC50) ranging from 26 to 41 nM. Conclusion: The predicted inhibitory effects of PF32 against both host and viral proteases may have synergistic effects for superior clinical efficacy.

A network pharmacology approach to assess the comparative pharmacodynamics of pharmaceutical excipient trehalose in human, mouse and rat

“…Advancements in bioinformatic and cheminformatic tools address these gaps by making it feasible to objectively assess the pharmacodynamic activity of excipients with selected species specificity. [41][42][43][44][45] This study highlights several pharmacodynamic features of trehalose which are relevant to its use in pharmaceutical formulations. The desirable physicochemical and pharmacokinetic properties of trehalose observed in this study are consistent with several previous in vivo studies [6,9,38,39,46,47] which validate its use as a pharmaceutical excipient.…”