In Silico prediction of biopharmaceutical features of remdesivir: A serendipitous drug for COVID-19

Background: Due to the novel nature of the Coronavirus Disease 2019 (COVID-19), there is limited or no standard treatment for it. Remdesivir, a drug originally developed against Ebola virus, is currently recommended for patients hospitalized with COVID-19. In spite of recent FDA assent of remdesivir as the only approved agent for COVID-19, there is limited information available about the physicochemical and pharmacokinetic (PK) properties of this drug. The objective of this in silico simulation work was to simulate the biopharmaceutical behavior of remdesivir.

Methods: The Spatial Data File format structures of remdesivir prodrug and nucleoside core were obtained from the PubChem database to upload on the GastroPlus software 9.7 version. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) Predictor and PKPlus modules were used to simulate physicochemical and PK properties, respectively, in healthy and predisposed patients.

Results: Remdesivir’s nucleoside core (GS-441524) was more hydrophilic than the inactive prodrug (GS-5734) with nucleoside core demonstrating better water solubility. Both had low blood brain barrier penetration while GS-5734 predicted to be 100% metabolized by CYP3A4. The bioavailability (Fa%, F%, C_max, C_maxLiver) of GS-5734 was higher than GS-441524. In addition, there was limited effect of renal function, liver function, weight, or age on the PK profile of remdesivir.

Conclusions: GS-5734 (inactive prodrug) appears to be a superior remdesivir derivative due to its hepatic stability, optimum hydrophilic/lipophilic nature, and disposition properties with limited effect of patient physiological conditions.

Acknowledgement: GastroPlus software 9.7 version was provided to S.D. by Simulations Plus, Inc. (Lancaster, CA) as an in-kind research support.