Oligomeric Conjugated Polyelectrolytes Display Site-Preferential Binding to an MS2 Viral Capsid

Martin, Tye D.; Hill, Eric H.; Whitten, David G.; Y., Eva; Evans, Deborah G.

doi:10.1021/acs.langmuir.6b01667

Cited by 14 publications

(17 citation statements)

References 49 publications

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“…When UV-light irradiation was used, the generation of corrosive reactive oxygen species induced strong damage to the capsid protein of the model viruses, thereby enhancing the antiviral activity of the studied OPEs ( Figure 12 ). MD simulations were used to understand the interactions at the molecular level between oligomers 18b , 19a , 23c , 24e , and 29 , and the MS2 protein capsid, and the findings confirmed the experimental observations [ 66 ]. These simulations showed the strong binding of such OPEs to the MS2 coat, which was significantly disrupted.…”

Section: Biocide Properties Of Opessupporting

confidence: 53%

A Portrait of the OPE as a Biological Agent

2021

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Oligophenylene ethynylenes, known as OPEs, are a sequence of aromatic rings linked by triple bonds, the properties of which can be modulated by varying the length of the rigid main chain or/and the nature and position of the substituents on the aromatic units. They are luminescent molecules with high quantum yields and can be designed to enter a cell and act as antimicrobial and antiviral compounds, as biocompatible fluorescent probes directed towards target organelles in living cells, as labelling agents, as selective sensors for the detection of fibrillar and prefibrillar amyloid in the proteic field and in a fluorescence turn-on system for the detection of saccharides, as photosensitizers in photodynamic therapy (due to their capacity to highly induce toxicity after light activation), and as drug delivery systems. The antibacterial properties of OPEs have been the most studied against very popular and resistant pathogens, and in this paper the achievements of these studies are reviewed, together with almost all the other roles held by such oligomers. In the recent decade, their antifungal and antiviral effects have attracted the attention of researchers who believe OPEs to be possible biocides of the future. The review describes, for instance, the preliminary results obtained with OPEs against severe acute respiratory syndrome coronavirus 2, the virus responsible for the COVID-19 pandemic.

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Section: Biocide Properties Of Opessupporting

confidence: 53%

A Portrait of the OPE as a Biological Agent

2021

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“…The ester-terminated series of PPE compounds is thus highly sensitive to detecting their solvation environment. The binding of dyes containing ethyl ester groups to proteins, likely mediated by hydrophobic interactions between protein residues and the hydrophobic backbone of the PPE compounds, 28 is indeed dramatically transduced to large increases in fluorescence (see Figure S6 and OPE1 spectra in Figure S7 ). As the molecular-level details of dye–protein interactions and influence of different substituents on the electronic properties of these structurally related dyes are unclear, further exploration is warranted.…”

Section: Resultsmentioning

confidence: 99%

Substituent, Charge, and Size Effects on the Fluorogenic Performance of Amyloid Ligands: A Small-Library Screening Study

Donabedian¹,

Evanoff

Monge³

et al. 2017

ACS Omega

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Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer’s and Parkinson’s diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure–function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin. A small library of 18 PPE compounds that vary in molecular weights, charge densities, water solubilities, and types and geometries of functional groups was tested. One compound, the small anionic oligo(p-phenylene ethynylene) electrolyte OPE1, was identified as a selective sensor for the amyloid conformation of both lysozyme and insulin. On the basis of protein binding and photophysical changes observed in the dye from this set of PPE compounds, keys to the selective detection of the amyloid protein conformation include moderate size, negative charge, and substituents that provide high microenvironment sensitivity to the fluorescence yield. These principles can serve as a guide for the further refinement of the effective amyloid-sensing molecules.

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“…We have shown in a previous simulation study that the binding of phenylene ethynylene-based oligomers to the MS2 virus capsid protein assembly is mediated by strong van der Waals interactions between the hydrophobic OPE backbone and the capsid protein and strong electrostatic interactions between the OPE charged side chains and charged residues on the capsid surface. 47 A combination of hydrophobic and electrostatic interactions between the oligomers and polymers and the SARS-CoV-2 spike proteins likely contribute to the compounds’ antiviral activities in this study. Of the 4 structural protein components, the membrane protein M is a likely target for both oligomers and polymers to bind and be in close proximity to interior RNA.…”

Section: Discussionmentioning

confidence: 86%

“…Both anionic (1 and 2) and cationic (3) oligomers are active; this is reasonable for non-covalent binding of the oligomers to protein components, likely the viral spike proteins, of the SARS-CoV-2. We have shown in a previous simulation study that the binding of phenylene ethynylene-based oligomers to the MS2 virus capsid protein assembly is mediated by strong van der Waals interactions between the hydrophobic OPE backbone and the capsid protein and strong electrostatic interactions between the OPE charged side chains and charged residues on the capsid surface 47. A combination of hydrophobic and electrostatic interactions between the oligomers and polymers and the SARS-CoV-2 spike proteins likely contribute to the compounds' antiviral activities in this study.…”

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confidence: 99%

Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers

Schanze

Whitten

Kell

et al. 2020

Preprint

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The current Covid-19 Pandemic caused by the highly contagious SARS-CoV-2 virus has proven extremely difficult to prevent or control. Currently there are few treatment options and very few long-lasting disinfectants available to prevent the spread. While masks and protective clothing and social distancing may offer some protection, their use has not always halted or slowed the spread. Several vaccines are currently undergoing testing; however there is still a critical need to provide new methods for inactivating the virus before it can spread and infect humans. In the present study we examined the inactivation of SARS-CoV-2 by synthetic conjugated polymers and oligomers developed in our laboratories as antimicrobials for bacteria, fungi and non-enveloped viruses. Our results show that we can obtain highly effective light induced inactivation with several of these oligomers and polymers including irradiation with near-UV and visible light. With both the oligomers and polymers, we can reach several logs of inactivation with relatively short irradiation times. Our results suggest several applications involving the incorporation of these materials in wipes, sprays, masks and clothing and other Personal Protection Equipment (PPE) that can be useful in preventing infections and the spreading of this deadly virus and future outbreaks from similar viruses.

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Oligomeric Conjugated Polyelectrolytes Display Site-Preferential Binding to an MS2 Viral Capsid

Cited by 14 publications

References 49 publications

A Portrait of the OPE as a Biological Agent

A Portrait of the OPE as a Biological Agent

Substituent, Charge, and Size Effects on the Fluorogenic Performance of Amyloid Ligands: A Small-Library Screening Study

Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers

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