Pharmacotherapeutic and Computational Approaches for Biopharmaceutical Considerations towards Drug Development and Delivery against COVID-19

The novel coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affected millions of people worldwide at an alarming rate. Moreover, the development of vaccines is still hope, but its camouflage mutations during transmission are still a challenge. In the dire condition of this pandemic, drug repurposing with the exploitation of computational modeling has become the cynosure to repurpose the already existing drugs such as remdesivir, Favipiravir, dexamethasone, and other drugs at clinical levels. Furthermore, their safety and efficacy against COVID-19 remain a challenge in different age groups and populations with pre-existing conditions like heart disease, hepatic and renal impairment, pregnancy, and immunocompromised states. Moreover, computational modeling allows studying physiological and biochemical parameters on drug transport, delivery, and therapeutic efficacy of dosage forms. This review explicitly provides a comprehensive account of the challenges and opportunities for developing physiologically based pharmacokinetic models (PBPK) and pharmacodynamic(PD) models to establish a therapeutic dosage regimen based on dose selection, safety, and efficacy. We also highlight the pharmacologic targeting strategies for ACE receptors, toxicity concerns, combination therapy, and drug-drug interactions for different repurposed drugs against COVID-19. In dreadful scenarios, PBPK and PD models hold promise for human PK and dose prediction in COVID-19, along with paving new horizons to improve the therapeutic as well as immuno-therapeutic efficacy using nano-drug delivery approaches, computer-aided drug design (CADD), and speed up clinical trials with a better understanding of quantitative in vitro to in vivo extrapolation (QIVIE) and established PK data.