Mechanosensing view of SARS-CoV-2 infection by a DNA nano-assembly

Zhang, Jialü; Huang, Yihao; Sun, Miao; Song, Tieying; Wan, Shuang; Yang, Chaoyong; Song, Yanling

doi:10.1016/j.xcrp.2022.101048

Cited by 11 publications

(11 citation statements)

References 48 publications

(72 reference statements)

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“…Susceptibility to mechanical stress sets a limit on potential applications of VLPs in various mucosal tissues. Mechanical agitation occurs during interactions with cells, e.g., during endocytosis or antigen presentation to B cells, in proximity to beating cilia or when sheared against the fecal stream. − Using different force probing techniques, the endocytosis “pulling” force exerted by a cell onto a virus, B cell antigen extraction, and the force of cilia agitation were measured to vary between a few to hundreds of pN. − Although this force range is generally below the yield force values of VLPs, when applied repeatedly as they do in vivo , they can disintegrate the capsids due to fatigue. − ,− As a result, enhancing the mechanical stability in the mucosal environment holds substantial translational relevance.…”

Section: Resultsmentioning

confidence: 99%

Surface Cross-Linking by Macromolecular Tethers Enhances Virus-like Particles’ Resilience to Mucosal Stress Factors

Ali,

Ganguillet,

Turgay

et al. 2024

ACS Nano

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Virus-like particles (VLPs) are emerging as nanoscaffolds in a variety of biomedical applications including delivery of vaccine antigens and cargo such as mRNA to mucosal surfaces. These soft, colloidal, and proteinaceous structures (capsids) are nevertheless susceptible to mucosal environmental stress factors. We cross-linked multiple capsid surface amino acid residues using homobifunctional polyethylene glycol tethers to improve the persistence and survival of the capsid to model mucosal stressors. Surface cross-linking enhanced the stability of VLPs assembled from Acinetobacter phage AP205 coat proteins in low pH (down to pH 4.0) and high protease concentration conditions (namely, in pig and mouse gastric fluids). Additionally, it increased the stiffness of VLPs under local mechanical indentation applied using an atomic force microscopy cantilever tip. Small angle X-ray scattering revealed an increase in capsid diameter after cross-linking and an increase in capsid shell thickness with the length of the PEG cross-linkers. Moreover, surface cross-linking had no effect on the VLPs' mucus translocation and accumulation on the epithelium of in vitro 3D human nasal epithelial tissues with mucociliary clearance. Finally, it did not compromise VLPs' function as vaccines in mouse subcutaneous vaccination models. Compared to PEGylation without cross-linking, the stiffness of surface cross-linked VLPs were higher for the same length of the PEG molecule, and also the lifetimes of surface crosslinked VLPs were longer in the gastric fluids. Surface cross-linking using macromolecular tethers, but not simple conjugation of these molecules, thus offers a viable means to enhance the resilience and survival of VLPs for mucosal applications.

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Section: Resultsmentioning

confidence: 99%

Surface Cross-Linking by Macromolecular Tethers Enhances Virus-like Particles’ Resilience to Mucosal Stress Factors

Ali,

Ganguillet,

Turgay

et al. 2024

ACS Nano

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“…Susceptibility to mechanical agitation was introduced as another limiting factor to VLP mucosal application. Using different force probing techniques, the endocytosis "pulling" force exerted by a cell onto a virus, B cell antigen extraction, and the force of cilia agitation were measured to vary between a few to hundreds of pN (44)(45)(46)(47)(48)(49)(50). Although this force range is generally below the yield force values of VLPs, when applied repeatedly as they do in vivo, they can disintegrate the capsids due to fatigue (16)(17)(18)(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Surface crosslinking of virus-like particles increases resistance to proteases, low pH, and mechanical stress for mucosal applications

Ahmed

Ganguillet

Turgay

et al. 2023

Preprint

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Virus-like particles (VLPs) are emerging as nano-scaffolds in a variety of biomedical applications including the delivery of vaccine antigens and therapeutic molecules. These soft, colloidal, and proteinaceous structures are nevertheless susceptible to environmental factors such as mechanical stress, proteases and low pH which limit their usefulness, particularly for mucosal applications. We addressed this issue by crosslinking multiple surface sites using polyethylene glycol linkers. Surface crosslinking enhanced the colloidal stability and mechanical strength of VLPs against pH, proteases, and mechanical stresses. Chemical crosslinking thus offers a viable means to enhance resilience of VLPs in mucosal applications.

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Section: Conflict Of Interest Statementmentioning

confidence: 99%

“…Song et al. constructed a platform (Virus‐TGT) for the mechanical force measurement of virus‐host cell interactions using a multivalence‐controlled aptamer and a series of DNA tension gauge tethers (TGT) [81] (Figure 10a). Specifically, the tetrahedral framework was used as the linker between the multivalent assembly of aptamer and TGT.…”

Section: Sars‐cov‐2 Aptamer‐based Diagnosis and Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Aptamer‐based strategies against SARS‐CoV‐2 viruses

Huang

Chen

Zhang

et al. 2023

BMEMat

Self Cite

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The COVID‐19 pandemic, caused by SARS‐CoV‐2, has seriously threatened human life and security in recent years and has had a serious impact on economic development. A range of strategies, including antibodies, small‐molecule agents and vaccines, have been developed and widely used to combat SARS‐CoV‐2. However, the uncertain development and susceptibility to mutation of SARS‐CoV‐2 pose challenges to these approaches, making it necessary to develop a broader range of strategies to complement and expand the diversity of attacks against SARS‐CoV‐2. As promising tools against SARS‐CoV‐2, aptamers have attracted wide attention due to their unique molecular properties. In this review, we survey SARS‐CoV‐2 aptamers and aptamer‐based detection tools as well as aptamer‐based therapeutics. In addition, we analyze the potential value of aptamers in the investigation of SARS‐CoV‐2 infection mechanism and vaccine design. Finally, we look forward to the future development direction of aptamers against SARS‐CoV‐2 or other viruses.

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Mechanosensing view of SARS-CoV-2 infection by a DNA nano-assembly

Cited by 11 publications

References 48 publications

Surface Cross-Linking by Macromolecular Tethers Enhances Virus-like Particles’ Resilience to Mucosal Stress Factors

Surface Cross-Linking by Macromolecular Tethers Enhances Virus-like Particles’ Resilience to Mucosal Stress Factors

Surface crosslinking of virus-like particles increases resistance to proteases, low pH, and mechanical stress for mucosal applications

Aptamer‐based strategies against SARS‐CoV‐2 viruses

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