Ligand concentration determines antiviral efficacy of silica multivalent nanoparticles.

Autor: Wang H; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland., Xu X; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland., Polla R; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland., Silva PJ; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland., Ong QK; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland., Stellacci F; Institute of Materials, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland; Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland; Global Health Institute, École Polytechnique Fédérale de Lausanne (EPFL), Station 12, CH-1015 Lausanne, Switzerland. Electronic address: francesco.stellacci@epfl.ch.
Jazyk: angličtina
Zdroj: Journal of colloid and interface science [J Colloid Interface Sci] 2024 Mar; Vol. 657, pp. 327-333. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1016/j.jcis.2023.11.122
Abstrakt: We have learned from the recent COVID-19 pandemic that the emergence of a new virus can quickly become a global health burden and kill millions of lives. Antiviral drugs are essential in our fight against viral diseases, but most of them are virus-specific and are prone to viral mutations. We have developed broad-spectrum antivirals based on multivalent nanoparticles grafted with ligands that mimic the target of viral attachment ligands (VALs). We have shown that when the ligand has a sufficiently long hydrophobic tail, the inhibition mechanism switches from reversible (virustatic) to irreversible (virucidal). Here, we investigate further how ligand density and particle size affect antiviral efficacy, both in terms of half-inhibitory concentration (IC 50 ) and of reversible vs irreversible mechanism. We designed antiviral silica nanoparticles modified with 11-mercaptoundecane-1-sulfonic acid (MUS), a ligand that mimics heparan sulfate proteoglycans (HSPG) and we showed that these nanoparticles can be synthesized with different sizes (4-200 nm) and ligand grafting densities (0.59-10.70 /nm 2 ). By testing these particles against herpes simplex virus type 2 (HSV-2), we show that within the size and density ranges studied, the antiviral IC 50 is determined solely by equivalent ligand concentration. The nanoparticles are found to be virucidal at all sizes and densities studied.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Stellacci reports a relationship with Asterivir AG that includes: board membership. Paulo Jacob Silva reports a relationship with Asterivir AG that includes: board membership and employment. Francesco Stellacci and Paulo Jacob Silva are co-founders of a start-up company that is developing antivirals, but not related to the topic of this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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