Pharmacophore Modeling and Binding Affinity of Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase.

Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba's compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = -8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = -7.84 kcal/mol; Ki = 7.96µM). From ashitaba's compounds, it was found that 4'-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxychalcone have low ΔG of below -6 kcal/mol. The lowest ΔG value was found in 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxy chalcone with a ΔG of -6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = -5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = -6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity.

Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review.

Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3-12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κß) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.

Multi Epitope-Based Vaccine Design for Protection Against Mycobacterium tuberculosis and SARS-CoV-2 Coinfection.

Background: A prophylactic and immunotherapeutic vaccine for Mycobacterium tuberculosis (MTB) and SARS-CoV-2 coinfection needs to be developed for a proactive and effective therapeutic approach. Therefore, this study aims to use immunoinformatics to design a multi-epitope vaccine for protection against MTB and SARS-CoV-2 coinfection. Methods: The bioinformatic techniques were used to screen and construct potential epitopes from outer membrane protein A Rv0899 of MTB and spike glycoprotein of SARS-CoV-2 for B and T cells. The antigenicity, allergenicity, and several physiochemical properties of the developed multi-epitope vaccination were then evaluated. Additionally, molecular docking and normal mode analysis (NMA) were utilized in evaluating the vaccine's immunogenicity and complex stability. Results: Selected proteins and predicted epitopes suggest that the vaccine prediction can be helpful in the protection against both SARS-CoV-2 and MTB coinfection. Through docking molecular and NMA, the vaccine-TLR4 protein interaction was predicted to be efficient with a high level of IgG, T-helper cells, T-cytotoxic cells, andIFN-γ. Conclusion: This epitope-based vaccine is a potentially attractive tool for SARS-CoV-2 and MTB coinfection vaccine development.