Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (M^pro)

ACS Omega, Journal Year: 2024, Volume and Issue: 9(32), P. 34196 - 34219

Published: Aug. 2, 2024

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), by SARS-CoV-2 its variants, further highlighted urgent need for development effective therapeutic agents. Currently, highly conserved broad-spectrum nature main proteases (M

Language: Английский

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A study on the effect of natural products against the transmission of B.1.1.529 Omicron

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 25, 2023

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by World Health Organization. However, large population is still unvaccinated, leading to emergence mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from Organization raised concerns about Omicron variant, which emerged South Africa during surge COVID-19 cases November 2021. Vaccines are not proven completely effective or safe against Omicron, clinical trials for combating infection virus. absence suitable pharmaceuticals has led scientists clinicians search alternative supplementary therapies, including dietary patterns, reduce effect strains. Main body This review analyzed aetiology, epidemiology, natural products Omicron. Although literature did include keywords related silico computational research, investigations were emphasized this study. Molecular docking was implemented compare interaction between Chloroquine with ACE2 receptor protein amino acid residues global proceeding SARS-CoV-2 also elucidated. results suggest that DGCG may bind three times more effectively than standard chloroquine. Conclusion variant highlighted need therapies impact current suggests such as be binding however, further research required validate study explore potential mitigate COVID-19. Graphical abstract

Language: Английский

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Comprehensive overview of different medicinal parts from Morus alba L.: chemical compositions and pharmacological activities

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 17, 2024

L., a common traditional Chinese medicine (TCM) with centuries-old medicinal history, owned various parts like Mori folium, ramulus, cortex and fructus. Different medical exhibit distinct modern pharmacological effects. folium exhibited analgesic, anti-inflammatory, hypoglycemic action lipid-regulation ramulus anti-bacterial, anti-asthmatic diuretic activities. showed counteraction of pain, inflammatory, bacterial, platelet aggregation. fructus could decompose fat, lower blood lipids prevent vascular sclerosis. The main chemical components in

Language: Английский

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In Silico Discovery of SARS-CoV-2 Main Protease Inhibitors Using Docking, Molecular Dynamics, and Fragment Molecular Orbital Calculations

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: 129(6), P. 1740 - 1749

Published: Jan. 31, 2025

The 3C-like protease of severe acute respiratory syndrome coronavirus 2, known as the main (Mpro), is an attractive drug target for treatment disease 2019. This study reports discovery novel Mpro inhibitors using several in silico techniques, including docking, molecular dynamics (MD), and fragment orbital (FMO) calculations. We performed docking calculations on 5950 compounds with bioactivity, 12 were selected. An enzymatic assay was conducted, revealing that BP-1-102 exhibits significant inhibitory activity IC50 11.1 μM. identification seed from experiments a few demonstrates effectiveness our Furthermore, detailed analyses MD FMO suggested interaction mechanism which hydroxyl group forms hydrogen bond E166 Mpro. SH-4-54, derivative without aforementioned group, investigated observed to be significantly reduced, 81.5 result strongly supports mechanism.

Language: Английский

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Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

ABSTRACT Severe coronavirus outbreaks, including SARS, MERS, and COVID‐19, have underscored the urgent need for effective antiviral therapies. This study evaluated activity of biflavanones isolated from Ouratea spectabilis —specifically ouratein (Our‐) A, B, C, D—against murine hepatitis virus (MHV‐3) human SARS‐CoV‐2. Cells infected with MHV‐3 or SARS‐CoV‐2 were treated ourateins, viral replication was assessed using plaque assays. Mice Our‐D either orally intraperitoneally. Key assessments included leukocyte counts, cytokine chemokine levels, histological analysis, survival rates. The mechanism action explored through in silico vitro studies focused on binding inhibition main protease (M pro ). significantly inhibited both viruses, a selective index 2.5 14.9 In vivo, reduced infiltration lungs, decreased CCL2 increased IL‐10, lowered plasma IL‐6 CXCL1 levels. Additionally, mitigated lung damage, partially restored betacoronavirus‐induced lymphopenia, loads heart, spleen, ultimately improving mice. revealed that Our‐A Our‐C had strong affinity M , vitro, unlike Our‐D. protected mice infection by modulating inflammatory response reducing loads, minimal effect inhibition, suggesting alternative mechanisms its activity.

Language: Английский

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Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: May 9, 2025

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the disease 2019 (COVID-19) pandemic, continues to pose global health challenges despite availability of approved vaccines and antiviral drugs. The emergence new variants SARS-CoV-2 ongoing post-COVID complications necessitate continuous exploration effective treatments. Kaurenoic acid (KA) a tetracyclic diterpenoid isolated from plants Copaifera genus has been previously recognized its anti-inflammatory, antibacterial, antifungal, antitumor properties. However, there lack knowledge about in vitro effects KA on viruses. Here, we evaluated effect replication first time. Methods Results demonstrated high selective index 16.1 against robust effectiveness B.1.617.2 (Delta) BA.2 (Omicron) variants. Mechanistically, was shown impair post-entry steps viral replication. In subgenomic replicon system, observed decrease RNA synthesis different cell lines. Using an infectious virus, larger reduction release virions observed. We suggest that interacts with proteases through molecular docking. Conclusion conclusion, emerges as inhibitor and, consequently, cycle. It could be good candidate further investigation clinical assays infection.

Language: Английский

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Repurposing of antimycobacterium drugs for COVID-19 treatment by targeting SARS CoV-2 main protease: An in-silico perspective

Gene, Journal Year: 2024, Volume and Issue: 922, P. 148553 - 148553

Published: May 10, 2024

Language: Английский

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Discovery of anti-SARS-CoV-2 secondary metabolites from the heartwood of Pterocarpus santalinus using multi-informative molecular networking

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: June 6, 2023

A pigment-depleted extract from the heartwood of Pterocarpus santalinus L. f. (PS-DE) showed promising anti-SARS-CoV-2 activity with an IC50 29.9 μg/mL in Caco-2-F03 cells. To determine potential active constituents within prior to isolation, multi-informative molecular network (MN) was applied. Therefore, separated by high-performance counter-current chromatography (HPCCC) into 11 fractions which were subsequently tested for and analysed UPLC-tandem mass spectrometry (MS2). The resulting MN combines bioactivity data MS2 data. analysis led targeted isolation seven compounds including one pterocarpan (7) reported first time as constituent P. four so far undescribed natural products (NPs) that belong compound classes arylpropanes (9), isoflavanones (10) coumestans (16) 3-arylcoumarins (17), respectively. In total, 15 synthetic isoflavonoid is structurally related metabolites activity. Thereby, two pterocarpans (-)-homopterocarpin (5) (-)-medicarpin (2), stilbene (E)-pterostilbene (1) 7-O-methylgenistein (11) a distinct antiviral values 17.2, 33.4, 34.7, 37.9 µM, respectively, no cytotoxic effects against cells (CC50 > 100 µM). addition, structure-activity relationship (SAR) proposed indicating structural requirements herein presented results support implementation networks powerful tool dereplication bioactive NPs.

Language: Английский

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Molecular networking unveils anti-SARS-CoV-2 constituents from traditionally used remedies

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 319, P. 117206 - 117206

Published: Sept. 30, 2023

Language: Английский

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Antiviral miliusanes and isolation of an unprecedented miliusane dimer from Miliusa balansae

Fitoterapia, Journal Year: 2024, Volume and Issue: 177, P. 106083 - 106083

Published: June 17, 2024

Language: Английский

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