Galangin for COVID-19

Objective: This study aims to elucidate the main compounds and mechanisms of action of Empon-empon (EE), a traditional Indonesian herb used for treating COVID-19 and atherosclerosis, utilizing an integrated network pharmacology and molecular docking approach. Methods: Active compounds in EE were obtained through the KNApSAcK, screening active compounds using parameters: oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. Compound-related target genes were collected from GeneCard, ChemBL, and Traditional Chinese Medicine Systems Pharmacology (TCMSP). Disease targets were obtained from the GeneCard database. The protein-protein interaction (PPI) network was built using STRING and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using ShinyGO. Molecular docking analysis using Autodock Vina in PyRx. Results: We identified 18 main compounds in EE. PPI analysis obtained 5 central EE targets involved in treating COVID-19 and atherosclerosis, namely E1A Binding Protein P300 (EP300), Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1), SRC Proto-Oncogene (SRC), Estrogen Receptor 1 (ESR1), and RELA Proto-Oncogene (RELA). GO and KEGG analysis illustrated EE's pharmacological effects through pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling, including Coronavirus disease. Catechin and quercetin exhibited the strongest binding affinity to EP300; licarin B and delphinidin to HSP90AA1; epicatechin and delphinidin to SRC; galangin and ellagic acid to ESR1; and guaiacin and licarin B to RELA. Conclusion: This research provides a strong foundation regarding the main compound and mechanism action of EE in treating atherosclerosis and COVID-19, suggesting potential as a novel therapeutic agent.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

COVID-19 pandemic is a serious problem in the world today. The SARS-CoV-2 virus that causes COVID-19 has important proteins used for its infection and development, namely the protease and spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010 program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBD-S (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities of bonds formed is represented as a docking score. The results show that hesperidin, one of the compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds perform inhibitory potential for the viral infection and replication. In general, the results of this study indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as prophylaxis of COVID-19.

The first cases of COVID-19, which is caused by the SARS-CoV-2, were reported in December 2019. The vertiginous worldwide expansion of SARS-CoV-2 caused the collapse of health systems in several countries due to the high severity of the COVID-19. In addition to the vaccines, the search for active compounds capable of preventing and/or fighting the infection has been the main direction of research. Since the beginning of this pandemic, some evidence has highlighted the importance of a phenolic-rich diet as a strategy to reduce the progression of this disease, including the severity of the symptoms. Some of these compounds (e.g., curcumin, gallic acid or quercetin) already showed capacity to limit the infection of viruses by inhibiting entry into the cell through its binding to protein Spike, regulating the expression of angiotensin-converting enzyme 2, disrupting the replication in cells by inhibition of viral proteases, and/or suppressing and modulating the host’s immune response. Therefore, this review intends to discuss the most recent findings on the potential of phenolics to prevent SARS-CoV-2.