Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile ; in silico and in Vitro assessments with structure-activity relationship

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(13), P. 6941 - 6953

Published: July 28, 2023

The proteolytic enzyme 3 C-like protease (3Clpro or M

Language: Английский

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Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 18, 2022

Purpose 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis maturation spike protein is essential for SARS-CoV-2 infection in vivo . The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the its variants. However, it not clear about mechanism treatment COVID-19. Therefore, this study used computer simulations to investigate COVID-19 by impeding infection. Methods GeneCards database was search gene targets, core targets were analyzed PPI, GO KEGG. Molecular docking molecular dynamics validate analyze binding stability small molecule target proteins. supercomputer platform simulate number hydrogen bonds, free energy, at residue level, radius gyration solvent accessible surface area. Results There 4,600 from database. KEGG analysis indicated signaling pathways immune response inflammation played crucial roles showed block treat acting on ACE2, NLRP3. demonstrate form very stable bindings with TLR7. Conclusion investigated simulation. We speculated may only inhibit invasion directly TMPRSS2, ACE2 DPP4, but also recognition process inflammatory regulating TLR7, NLRP3 IL-10 invasion. these results suggested act through multiple reduce damage responses.

Language: Английский

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Efficacy of Bromhexine versus Standard of Care in Reducing Viral Load in Patients with Mild-to-Moderate COVID-19 Disease Attended in Primary Care: A Randomized Open-Label Trial

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 12(1), P. 142 - 142

Published: Dec. 24, 2022

A 28-day randomized open-label multicenter study was conducted to assess the efficacy of bromhexine plus standard care (SOC) (n = 98) vs. SOC alone 93) in 191 outpatients with mild-to-moderate COVID-19 primary health setting. Bromhexine three daily doses 10 mL (48 mg/day) were administered for seven days. The endpoint reduction viral load estimated as cycle thresholds (Ct) detect ORF1ab, N Protein, and S Protein genes by RT-qPCR saliva samples on day 4 compared baseline. Ct values increased from baseline throughout days 14 (p < 0.001) but significant differences between groups not found. Differences percentages patients low, medium, high loads at 4, 7, found either. In summary, treatment SCO associated a which significantly different than similar reductions observed alone. present findings do seem favor use an antiviral COVID-19.

Language: Английский

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In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein

Molecules, Journal Year: 2022, Volume and Issue: 27(24), P. 8957 - 8957

Published: Dec. 15, 2022

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug is crucial along vaccinations to decrease cases. A potential target such antivirals could be membrane components causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening crude extracts seven ethnomedicinal plants receptor-binding domain (S1-RBD) SARS-CoV-2 using enzyme-linked immunosorbent assay (ELISA). Following encouraging results Tinospora cordifolia, silico studies were conducted 14 reported secondary metabolites isolated from T. cordifolia—a species widely cultivated and used as Himalayan country Nepal—using Genetic Optimization Ligand Docking (GOLD), Molecular Operating Environment (MOE), BIOVIA Discovery Studio. The molecular docking binding energy study revealed cordifolioside-A had a higher affinity was most competitive site dynamics (MD) simulation GROMACS 5.4.1 further assayed interaction between potent compound sites It demonstrated better stability, resulted conformational change S1-RBD, hence hindering activities addition, ADMET analysis cordifolia promising pharmacokinetic properties. Our thus recommends certain possible medicinal candidates SARS-CoV-2.

Language: Английский

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KDM5 Family Demethylase Inhibitor KDOAM-25 Reduces Entry of SARS-CoV-2 Pseudotyped Viral Particles into Cells

Bulletin of Experimental Biology and Medicine, Journal Year: 2023, Volume and Issue: 175(1), P. 150 - 156

Published: May 1, 2023

Language: Английский

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