ABSTRACT
Lianhuaqingwen (LH), one traditional Chinese medicine (TCM), has been used to treat the coronavirus disease 2019 (COVID-19), but its ecotoxicity with potential human health security has not been well investigated. To overcome such adverse effects and improve its medication efficacy, an intelligent multi-method integrated dietary scheme, screening, and performance evaluation approach was developed. Thirteen LH compounds were selected, and the main protease (Mpro) was used as the potential drug target. Resulted information showed that the more compounds of LH added, the higher medication efficacy obtained using multi-method integrated screening system, expert consultation method, and molecular dynamics simulation. Pharmacodynamic mechanism analysis showed that low total energy and polar surface area of LH active compound (i.e., ß-sitosterol) will contribute to the best therapeutic effect on COVID-19 using quantitative structure-activity relationships (QSAR) and sensitivity models. Additionally, when mild COVID-19 patients take LH with the optimum dietary scheme (i.e., ß-lactoglobulin, α-lactalbumin, vitamin A, vitamin B, vitamin C, carotene, and vitamin E), the medication efficacy were significantly improved (23.58%). Pharmacokinetics and toxicokinetics results showed that LH had certain human health risks and ecotoxicity. This study revealed the multi-compound interaction mechanism of LH treatment on COVID-19, and provided theoretical guidance for improving therapeutic effect, evaluating TCM safety, and preventing human health risk.