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.