Impact of Drug Metabolism/Pharmacokinetics and its Relevance Considering Traditional Medicine-based Anti-COVID-19 Drug Research

Abstract

Background: The representative anti-COVID-19 herbs, i.e. Poria cocos, Pogostemon, Prunus, and Glycyrrhiza plants, are commonly used in the prevention and treatment of COVID-19, a pandemic caused by SARS-CoV-2. Diverse medicinal compounds with favorable anti-COVID-19 activities are abundant in these plants, and their unique pharmacological/pharmacokinetic properties are being revealed. However, the current trends of drug metabolism/pharmacokinetic (DMPK) investigations of anti-COVID-19 herbs have not been systematically summarized. Methods: Here, the latest awareness, as well as the perception gaps of DMPK attributes, in the anti-COVID-19 drug development and clinical usage was elaborated and critically commented. Results: The extracts and compounds of P. cocos, Pogostemon, Prunus, and Glycyrrhiza plants show distinct and diverse absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties. The complicated herb-herb interactions (HHIs) and herb-drug interactions (HDIs) of anti-COVID-19 Traditional Chinese Medicine (TCM) herb pair/formula dramatically influence the PK/pharmacodynamic (PD) performance of compounds thereof, which may inspire researchers to design innovative herbal/compound formulas for optimizing the therapeutic outcome of COVID-19 and related epidemic diseases. The ADME/T of some abundant compounds in anti-COVID-19 plants have been elucidated, but DMPK studies should be extended to more compounds of different medicinal parts, species and formulations, and would be facilitated by various omics platforms and computational analyses. Conclusion: In the framework of systems pharmacology and pharmacophylogeny, the DMPK knowledge base would promote the translation of bench findings into the clinical practice of anti-COVID-19, and speed up the anti-COVID-19 drug discovery and development.

Deepening insights into food and medicine continuum within the context of pharmacophylogeny

“…In contrast to these advances, the pharmacokinetic/pharmacodynamic (PKPD) studies of these FMC materials are far less enough, and there is gap in the awareness of absorption, distribution, metabolism, excretion and toxicity (ADMET) attributes of many FMC products. Despite numerous reports about beneficial effects of FMC materials, it is difficult to determine the chemical basis of different therapeutic and health effects, for which studies of ADMET properties must be taken into account, including the elucidation of gut microbiota mediated transformation ( Hao et al, 2022b ). The phylogenetically closer species are more likely to have similar phytometabolome, but FMC chemicals with the same/similar structural type might have analogous or reverse ADMET properties, which warrant case-by-case elaborations in the context of pharmacophylogeny.…”

“…Clinical trials are yet to be done to manifest the claimed health benefits. Of note, most FMC studies focus on either in vitro screening in cell culture or network pharmacology speculations based on data from in silico and/or simple cell culture models ( Hao et al, 2022b ). In the future, the clinical trials of FMC products have to be conducted as open label with placebo, covering enough number of subjects, and should focus on symptomatic benefits.…”

High‐quality trials and pharmacological studies needed as translational evidence for the application of traditional Chinese medicine Lianhua Qingwen against COVID‐19

“…Such crude breakdown of research papers on this subject clearly suggests a lack of robust validation, with overpopulated reviews based on a small number of highly heterogeneous original studies of varied quality. The larger chunk of the reports came up from the search were either in vitro screening in cell culture or network pharmacological speculations based on data from in silico and/or simple cell culture models, without much needed consideration of the complex pharmacodynamic and pharmacokinetic (PDPK) processes after oral intake of TCM medications (Hao, Wang, & Xiao, 2022 ). The few clinical trials were conducted as open label without placebo, covering low number of subjects, and mainly focused on symptomatic benefits (Liang et al, 2021 ).…”

Editorial: Plant-derived natural compounds in drug discovery: The prism perspective between plant phylogeny, chemical composition, and medicinal efficacy

“…Pharmacophylogeny successfully guides the development of novel curative taxa (Hao and Xiao, 2020), while circumventing the limitations of old-style approaches and enabling the targeted studies. In contrast, the random discovery (accidental discovery) relies too much on luck; new molecular entities obtained by combinatorial chemistry, high throughput screening or computer aided drug design very often fail due to improper pharmacokinetic and pharmacodynamic properties (Hao et al, 2022c). A complete knowledgebase of chemodiversity/ phytometabolism of systematic groups of interest is an essential base for pharmacophylogeny.…”

“…Many medicinally important phytometabolites, e.g., alkaloids, terpenoids and phenylpropanoids, can be further subdivided structurally, and the phylogenetic signals of different subtypes/subclasses could be distinct. For compounds with similar structures, not only the resemblances and variances of their bioactivities should be explored, but also those of their pharmacokinetic and pharmacodynamic properties should be clarified one by one (Hao et al, 2022c). Therefore, there is a great deal of work to be conducted on various topics of pharmacophylogeny.…”