Singlet oxygen effects on lipid membranes: implications for the mechanism of action of broad-spectrum viral fusion inhibitors

2014 ◽  
Vol 459 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Axel Hollmann ◽  
Miguel A. R. B. Castanho ◽  
Benhur Lee ◽  
Nuno C. Santos
Keyword(s):  
Singlet Oxygen ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Lipid Membranes ◽  
Cell Membranes ◽  
Viral Fusion ◽  
Fusion Inhibitors ◽  
Oxygen Effects

By studying the interaction of LJ001 and JL103 with lipid membranes, we demonstrate that singlet oxygen produced by both compounds induces changes on lipid properties, preventing the fusion between viral and cell membranes.

scholarly journals New Broad-Spectrum Viral Fusion Inhibitors Act by Deleterious Effect on the Viral Membrane through the Production Singlet Oxygen Molecules

2014 ◽  
Vol 106 (2) ◽  
pp. 708a
Author(s):  
Axel Hollmann ◽  
Marcelo T. Augusto ◽  
Sonia Gonçalves ◽  
Frederic Vigant ◽  
Miguel A.R.B. Castanho ◽  
...  
Keyword(s):  
Singlet Oxygen ◽  
Broad Spectrum ◽  
Deleterious Effect ◽  
Viral Fusion ◽  
Viral Membrane ◽  
Fusion Inhibitors

scholarly journals Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture

2015 ◽  
Vol 11 (5) ◽  
pp. 1163-1167 ◽  
Author(s):  
Axel Hollmann ◽  
Sónia Gonçalves ◽  
Marcelo T. Augusto ◽  
Miguel A.R.B. Castanho ◽  
Benhur Lee ◽  
...  
Keyword(s):  
Singlet Oxygen ◽  
Broad Spectrum ◽  
Fusion Inhibitor ◽  
Viral Fusion

scholarly journals Effects of lipid heterogeneity on model human brain lipid membranes

Soft Matter ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. 126-135
Author(s):  
Sze May Yee ◽  
Richard J. Gillams ◽  
Sylvia E. McLain ◽  
Christian D. Lorenz
Keyword(s):  
Human Brain ◽  
Lipid Membranes ◽  
Cell Membranes ◽  
Brain Lipid ◽  
Lipid Distribution

Cell membranes naturally contain a heterogeneous lipid distribution.

Elucidation of molecular interactions between lipid membranes and ionic liquids using model cell membranes

Soft Matter ◽  
2012 ◽  
Vol 8 (20) ◽  
pp. 5501 ◽  
Author(s):  
Seunghwan Jeong ◽  
Sung Ho Ha ◽  
Sang-Hyun Han ◽  
Min-Cheol Lim ◽  
Sun Min Kim ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
Molecular Interactions ◽  
Lipid Membranes ◽  
Cell Membranes ◽  
Model Cell

Brilacidin, a COVID-19 Drug Candidate, demonstrates broad-spectrum antiviral activity against human coronaviruses OC43, 229E and NL63 through targeting both the virus and the host cell

2021 ◽  
Author(s):  
Yanmei Hu ◽  
Hyunil Jo ◽  
William DeGrado ◽  
Jun Wang
Keyword(s):  
Antiviral Activity ◽  
Cell Surface ◽  
Host Cell ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Drug Candidate ◽  
Host Defense Peptides ◽  
Antibiotic Drug ◽  
Host Cell Surface ◽  
Human Coronaviruses

Brilacidin, a mimetic of host defense peptides (HDPs), is currently in phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against SARS-CoV-2 by inactivating the virus. In this work, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, a HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.

Peptide-based Fusion Inhibitors for Preventing the Six-helix Bundle Formation of Class I Fusion Proteins: HIV and Beyond

2021 ◽  
Vol 19 ◽  
Author(s):  
Ajit Monteiro ◽  
Karl O. A. Yu ◽  
Mark D. Hicar
Keyword(s):  
Fusion Proteins ◽  
Class I ◽  
European Medicines Agency ◽  
Viral Fusion ◽  
Helix Bundle ◽  
Fusion Inhibitors ◽  
Current State ◽  
Hiv Research ◽  
Inhibitor Drug ◽  
Combination Regimens

: A number of different viral families have developed convergent methods to infect cells. Class I fusion proteins are commonly used by members of Arenaviridae, Coronaviridae, Filovirdae, Orthomyxoviridae, Paramyxoviridae, and Retroviridae. Class I viral fusion proteins are trimers that are involved in recognizing the cellular receptor, with a region that is responsible for fusing the viral and target cell membranes. During the fusion process, the fusion region folds into a six-helix bundle (6HB) which approximates the two membranes leading to fusion. For human immunodeficiency virus (HIV), the gp41 subunit is responsible for the formation of this 6HB. The fusion inhibitor drug enfuvirtide, or T20, is the only US Food and Drug Administration and European Medicines Agency approved drug which targets this crucial step and has been widely used in combination regimens for the treatment of HIV since March 2003. In this review, we describe the current state of peptide-based fusion inhibitors in the treatment of HIV, and review how the field of HIV research is driving advances in the development of similar therapeutics in other viral systems, including the severe acute respiratory syndrome (SARS) coronaviruses.

scholarly journals An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals

Redox Biology ◽  
2020 ◽  
Vol 36 ◽  
pp. 101601
Author(s):  
Lei Zeng ◽  
Meng-Di Wang ◽  
Sheng-Li Ming ◽  
Guo-Li Li ◽  
Peng-Wei Yu ◽  
...  
Keyword(s):  
Lipid Oxidation ◽  
Singlet Oxygen ◽  
Broad Spectrum ◽  
New Paradigm

Ag-Conjugated graphene quantum dots with blue light-enhanced singlet oxygen generation for ternary-mode highly-efficient antimicrobial therapy

2020 ◽  
Vol 8 (7) ◽  
pp. 1371-1382 ◽  
Author(s):  
Yunjian Yu ◽  
Lin Mei ◽  
Yanmei Shi ◽  
Xinge Zhang ◽  
Kesong Cheng ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Singlet Oxygen ◽  
Blue Light ◽  
Silver Nanoparticle ◽  
Broad Spectrum ◽  
Antimicrobial Therapy ◽  
Graphene Quantum Dots ◽  
Oxygen Generation ◽  
Singlet Oxygen Generation ◽  
Highly Efficient

A broad-spectrum antibacterial system was produced in which silver nanoparticle-conjugated graphene quantum dots were utilised as a blue light-enhanced nanotherapeutic for efficient ternary-mode antimicrobial therapy.

scholarly journals Orally Active Fusion Inhibitor of Respiratory Syncytial Virus

2004 ◽  
Vol 48 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Christopher Cianci ◽  
Kuo-Long Yu ◽  
Keith Combrink ◽  
Ny Sin ◽  
Bradley Pearce ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lipid Membranes ◽  
Syncytium Formation ◽  
Single Amino Acid ◽  
Fusion Inhibitors ◽  
Amino Acid Mutations ◽  
Syncytial Virus ◽  
20 Nm ◽  
Orally Active

ABSTRACT BMS-433771 was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. It exhibited excellent potency against multiple laboratory and clinical isolates of both group A and B viruses, with an average 50% effective concentration of 20 nM. Mechanism-of-action studies demonstrated that BMS-433771 inhibits the fusion of lipid membranes during both the early virus entry stage and late-stage syncytium formation. After isolation of resistant viruses, resistance was mapped to a series of single amino acid mutations in the F1 subunit of the fusion protein. Upon oral administration, BMS-433771 was able to reduce viral titers in the lungs of mice infected with RSV. This new class of orally active RSV fusion inhibitors offers potential for clinical development.

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