COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that can be modified to become a specific antiviral compound with markedly improved potency against different viruses, such as the influenza virus. In this study, we have identified a collection of aloperine derivatives that can inhibit the entry of SARS-CoV-2 into host cells. Compound is the most potent tested aloperine derivative that inhibited the entry of SARS-CoV-2 (D614G variant) spike protein-pseudotyped virus with an IC of 0.5 µM. The compound was also active against several other SARS-CoV-2 variants including Delta and Omicron. Results of a confocal microscopy study suggest that compound inhibited the viral entry before fusion to the cell or endosomal membrane. The results are consistent with the notion that aloperine is a privileged scaffold that can be used to develop potent anti-SARS-CoV-2 entry inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455918 | PMC |
| http://dx.doi.org/10.3390/ijms23179659 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Host factor DIAPH1 regulates pseudorabivirus replication by modulating the dynamics of cytoskeleton.
Int J Biol Macromol
January 2025
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China. Electronic address:
As obligate parasites, viruses exploit host cell organelles and molecular components to complete their life cycle. Among which, viruses firstly hijack the cytoskeleton of host cells to ensure their efficiently cell entry and replication. Although formin family members play a key role in both microfilament and microtubule cytoskeletal remodeling, few studies addressed the detailed function and mechanism of formins in the process of viral infection.
View Article and Find Full Text PDFMolecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.
CNS Neurosci Ther
January 2025
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, USA.
Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration.
View Article and Find Full Text PDFSulfated Glycosaminoglycans as Inhibitors for Chlamydia Infections: Molecular Weight and Sulfation Dependence.
Macromol Biosci
January 2025
Heinrich- Heine- University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Organic Chemistry and Macromolecular Chemistry, 40204, Düsseldorf, Germany.
Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs.
View Article and Find Full Text PDFStimulation of IRES-Dependent Translation by Rocaglamide A Increases the Replication and Virulence of Cricket Paralysis Virus in Lepidopteran Insect Cells.
Arch Insect Biochem Physiol
January 2025
Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
The discovery that infections of viruses are pervasive among insects has considerable potential for future applications, such as new strategies for pest control through the manipulation of virus-host interactions. However, few studies can be found that aim to minimize (for beneficial insects) or maximize (for pests) virus impact or virulence. Viruses generally employ molecular mechanisms that deviate from the cells' to increase their replication efficiency and to avoid the immune response.
View Article and Find Full Text PDFGreen Synthesis of Tetrahydropyrazino[2,1-a:5,4-a']diisoquinolines as SARS-CoV-2 Entry Inhibitors.
ACS Omega
January 2025
Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
A class of tetrahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives were synthesized under environmentally friendly conditions using water as the solvent. The 3-D structures of some synthesized compounds were determined by X-ray diffraction. Since naturally occurring isoquinoline alkaloids have significant antiviral activities against a wide range of viruses, including coronaviruses, the synthesized compounds were assayed for their inhibitory activities against SARS-CoV-2.
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!