Background: The recent outbreak of Coronavirus SARS-CoV-2 (Covid-19), which has rapidly spread around the world in about three months with tens of thousands of deaths recorded so far is a global concern. An urgent need for potential therapeutic intervention is of necessity. M is an attractive druggable target for the development of anti-COVID-19 drug development.
Methods: Compounds previously characterized by Melissa officinalis were queried against the main protease of coronavirus SARS-CoV-2 using a computational approach.
Results: Melitric acid A and salvanolic acid A had higher affinity than lopinavir and ivermectin using both AutodockVina and XP docking algorithms. The computational approach was employed in the generation of the QSAR model using automated QSAR, and in the docking of ligands from Melissa officinalis with SARS-CoV-2 Mpro inhibitors. The best model obtained was KPLS_Radial_ 28 (R = 0.8548 and Q=0.6474, which was used in predicting the bioactivity of the lead compounds. Molecular mechanics based MM-GBSA confirmed salvanolic acid A as the compound with the highest free energy and predicted bioactivity of 4.777; it interacted with His-41 of the catalytic dyad (Cys145-His41) of SARS-CoV-2 main protease (M), as this may hinder the cutting of inactive viral protein into active ones capable of replication.
Conclusion: Salvanolic acid A can be further evaluated as a potential M inhibitor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1570163817999200918103705 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Prostate-specific antigen testing in the United States during 2008-2022 in relation to the US preventive services task force recommendations.
Sci Rep
December 2024
Department of Public Health, College of Life Sciences, Brigham Young University, 2063 Life Sciences Building, Provo, UT, 84602, USA.
The prevalence of prostate-specific antigen (PSA) testing has consistently fallen for several years. This study explored how the decreasing trend differs by selected variables and reasons for taking the PSA test. Analyses involved men, aged 40 years or older, who completed the Behavior Risk Factor Surveillance System (BRFSS) survey in even number years from 2008 through 2022.
View Article and Find Full Text PDFCatalytic Mechanism of SARS-CoV-2 3-Chymotrypsin-Like Protease as Determined by Steady-State and Pre-Steady-State Kinetics.
ACS Catal
December 2024
Departments of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.
The 3-chymotrypsin-like protease (3CL-PR; also known as Main protease) of SARS-CoV-2 is a cysteine protease that is the target of the COVID-19 drug, Paxlovid. Here, we report for 3CL-PR, the pH-rate profiles of a substrate, an inhibitor, affinity agents, and solvent kinetic isotope effects (sKIEs) obtained under both steady-state and pre-steady-state conditions. "Bell-shaped" plots of log( / ) vs pH for the substrate (Abz)SAVLQ*SGFRK(Dnp)-NH and p vs pH for a peptide aldehyde inhibitor demonstrated that essential acidic and basic groups of p = 8.
View Article and Find Full Text PDFSLP2 and MIC13 synergistically coordinate MICOS assembly and crista junction formation.
iScience
December 2024
Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Duesseldorf, Germany.
The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging.
View Article and Find Full Text PDFCausal effects of circulating lipids and lipid-lowering drugs on the risk of atopic dermatitis: a mendelian randomization study.
Arch Dermatol Res
December 2024
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shannxi, China.
Lipid metabolism disorders are frequently noted in atopic dermatitis (AD) patients, prompting the long-term use of lipid-lowering drugs. However, the causal effects of circulating lipids and different lipid-lowering drugs on the risk of AD are not thoroughly understood. Using publicly available genome-wide association studies (GWAS) summary data from two different cohorts, a series of Mendelian randomization (MR) analyses were conducted to explore the causal effects of genetically proxied circulating lipids and lipid-lowering drugs on the risk of AD.
View Article and Find Full Text PDFSimulated Gastrointestinal Fluids Impact the Stability of Polymer-Functionalized Selenium Nanoparticles: Physicochemical Aspects.
Int J Nanomedicine
December 2024
Division of Medical Physics and Biophysics, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, 8010, Austria.
Background: Selenium (Se) is a vital micronutrient for maintaining homeostasis in the human body. Selenium nanoparticles (SeNPs) have demonstrated improved bioavailability compared to both inorganic and organic forms of Se. Therefore, supplementing with elemental Se in its nano-form is highly promising for biomedical applications related to Se deficiency.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!