Abbreviated Profile of Drugs (APOD): modeling drug safety profiles to prioritize investigational COVID-19 treatments

Highlights

• Drugs with only strong and moderate safety profiles can be repurposed for COVID-19 or any other disease targets.

• The existing effective drugs with weak safety profiles can be modified into effective drugs with moderate/strong profiles.

• Unification, uniformity, and integration of drug properties by the APOD method represents an advancement in drug discovery.

Abstract

Safe and effective oral formulation of a drug, that is easy to store, transport, and administer, is imperative to reach the masses including those without adequate facilities and resources, in order to combat globally transmitted coronavirus disease 2019 (COVID-19). In this decision analytic modeling study, the safety of investigational COVID-19 drugs in clinical trials was assessed using the Abbreviated Profile of Drugs (APOD) methodology. The method was extensively tested for various unbiased datasets based on different criteria such as drugs recalled worldwide for failing to meet safety standards, organ-specific toxicities, cytochrome P450 inhibitors, and Food and Drug Administration (FDA) approved drugs with remarkable successes. Experimental validation of the predictions made by APOD were demonstrated by comparison with a progression of multiparametric optimization of a series of cancer drugs that led to a potent drug (GDC-0941) which went into the clinical development. The drugs were classified into three categories of safety profiles: strong, moderate and weak. A total of 3556 drugs available in public databases were examined. According to the results, drugs with strong safety profiles included molnupiravir (EIDD-2801), moderate safety profiles included dexamethasone, and weak safety profiles included lopinavir. In this analysis, the physicochemical-pharmacokinetic APOD fingerprint was associated with the drug safety profile of withdrawn, approved, as well as drugs in clinical trials and the APOD method facilitated decision-making and prioritization of the investigational treatments.