ABSTRACT
Purpose: This study aimed to screen potential drug candidates from the flavonoids of the genus Erythrina for the Corona Virus Disease 2019 (COVID-19) treatment. Patients and Methods: A comprehensive screening was conducted on the structures of 473 flavonoids derived from the genus Erythrina, focusing on their potential toxicity and pharmacokinetic profiles. Subsequently, flavonoids that were non-toxic and possessed favorable pharmacokinetic properties underwent further analysis to explore their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor, employing molecular docking and molecular dynamics simulations. Results: Among 473 flavonoids, 104 were predicted to be safe from being mutagenic, hepatotoxic, and inhibitors of the human ether-a-go-go-related gene (hERG). Among these 104 flavonoids, 18 compounds were predicted not to be substrates of P-glycoprotein (P-gp). Among these 18 flavonoids, gangetinin (471) and erybraedin D (310) exhibit low binding affinities and root mean square deviation (RMSD) values, indicating stable binding to the ACE2 receptor. The physicochemical attributes of compounds 310 and 471 suggest that they possess drug-like properties. Conclusion: Gangetinin (471) and erybraedin D (310) may serve as promising candidates for COVID-19 treatment due to their potential to inhibit the ACE2-RBD interaction. This warrants further investigation into their inhibitory effects on ACE2-RBD binding through in vitro experiments.
ABSTRACT
The emergence of antimicrobial resistance due to the widespread and inappropriate use of antibiotics has now become the global health challenge. Flavonoids have long been reported to be a potent antimicrobial agent against a wide range of pathogenic microorganisms in vitro. Therefore, new antibiotics development based on flavonoid structures could be a potential strategy to fight against antibiotic-resistant infections. This research aims to screen the potency of flavonoids of the genus Erythrina as an inhibitor of bacterial ATPase DNA gyrase B. From the 378 flavonoids being screened, 49 flavonoids show potential as an inhibitor of ATPase DNA gyrase B due to their lower binding affinity compared to the inhibitor and ATP. Further screening for their toxicity, we identified 6 flavonoids from these 49 flavonoids, which are predicted to have low toxicity. Among these flavonoids, erystagallin B (334) is predicted to have the best pharmacokinetic properties, and therefore, could be further developed as new antibacterial agent.
