Daphnoretin from Carthamus tinctorius as a Potential Inflammatory Inhibitor in COVID-19 by Binding to Toll-like Receptor-4: An in silico Molecular Docking Study

Lismayana Hansur; Melva Louisa; Puspita Eka Wuyung; Fadilah Fadilah

doi:10.3889/oamjms.2022.7961

Authors

Lismayana Hansur Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Microbiology, Faculty of Medicine, Universitas Muhammadiyah Makassar, Makassar, Indonesia
Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Puspita Eka Wuyung Department of Pathological Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Animal Research Facility, Indonesian Medical Education and Research Institute, Universitas Indonesia, Jakarta, Indonesia
Fadilah Fadilah Department of Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Bioinformatics Core Facilities Cluster, Indonesian Medical Education and Research Institute (IMERI), Universitas Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.7961

Keywords:

Cytokine storm, FcγRIIa, Flavonoids, Rutin, SARS-CoV2

Abstract

BACKGROUND: Cytokine storm in COVID-19 patients has contributed to many morbidities and mortalities in patients. Studies have found that toll-like receptors (TLRs) and some Fc receptors play essential roles in the hyperactivation of the immune system. Up to date, researchers are still in progress to discover effective and safe drugs to alleviate the hyperinflammatory state in COVID-19. The previous studies had shown that Carthamus tinctorius and its bioactive compounds might have anti-inflammatory activities in animal models.

AIM: We aimed to investigate the possible interactions of several flavonoids from C. tinctorius with several immune system components using a biocomputational approach.

METHODS: Molecular docking was done using the AutoDock program based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) COVID-19 pathway. The most suitable receptors found were studied to study the interactions with several flavonoids from C. tinctorius.

RESULTS: TLR4, TLR8, and FcγRIIa were found to bind with SARS CoV2 inflammatory pathway and further selected as macromolecules for potential interactions study with 22 flavonoids from C. tinctorius. Of the 22 flavonoids studied, daphnoretin showed the best binding affinity with TLR4 and Rutin was shown to attach best with FcγRIIa. Unlike its excellent binding to TLR4, daphnoretin showed weak binding to TLR8.

CONCLUSION: Daphnoretin showed an excellent affinity with TLR4 and might be a good candidate as an inhibitor in hyperinflammatory reactions in COVID-19 DTLR8.

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