6 documents found, page 1 of 1
2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), in...
Kuhn, Jens H; Adkins, Scott; Alioto, Daniela; Alkhovsky, Sergey V; Amarasinghe, Gaya K; Anthony, Simon J; Avsic-Zupanc, Tatjana; Ayll?n, Mar?a AThis work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This project has been funded in whole or i...
Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor ...
Hollmann, Axel; Gonçalves, Sónia; Augusto, Marcelo T.; Castanho, Miguel A. R. B.; Lee, Benhur; Santos, Nuno C.Targeting membranes of enveloped viruses represents an exciting new paradigm to explore on the development of broad-spectrum antivirals. Recently, broad-spectrum small-molecule antiviral drugs were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus–cell fusion. Those compounds, including an oxazolidine-2,4-dithione named JL103 that presented the most promis...
Broad-spectrum antivirals against viral fusion
Vigant, Frederic; Santos, Nuno C.; Lee, BenhurEffective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re emerging infectious diseases are ...
The rigid amphipathic fusion Inhibitor dUY11 acts through photosensitization of...
Vigant, Frederic; Hollmann, Axel; Lee, Jihye; Santos, Nuno C.; Jung, Michael E.; Lee, BenhurRigid amphipathic fusion inhibitors (RAFIs) are lipophilic inverted-cone-shaped molecules thought to antagonize the membrane curvature transitions that occur during virus-cell fusion and are broad-spectrum antivirals against enveloped viruses (Broad-SAVE). Here, we show that RAFIs act like membrane-binding photosensitizers: their antiviral effect is dependent on light and the generation of singlet oxygen (1O2),...
Singlet oxygen effects on lipid membranes : implications for the mechanism of a...
Hollmann, Axel; Castanho, Miguel A. R. B.; Lee, Benhur; Santos, Nuno C.It was reported recently that a new aryl methyldiene rhodamine derivative, LJ001, and oxazolidine-2,4-dithione, JL103, act on the viral membrane, inhibiting its fusion with a target cell membrane. The aim of the present study was to investigate the interactions of these two active compounds and an inactive analogue used as a negative control, LJ025, with biological membrane models, in order to clarify the mecha...
A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion
Vigant, Frederic; Lee, Jihye; Hollmann, Axel; Tanner, Lukas B.; Ataman, Zeynep Akyol; Yun, Tatyana; Shui, Guanghou; Aguilar, Hector C.; Zhang, DongLJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50≤0.5 mM), and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001’s specific inhibition of viruscell fusion. The antiviral activity of LJ001 was light...