Herpes Simplex Virus-1 infection in human primary corneal epithelial cells is blocked by a stapled peptide that targets processive DNA synthesis

Guan, Hancheng; Nuth, Manunya; Lee, Vivian; Lin, Chenyan; Mitchell, Claire H.; Lu, WenNan; Scott, Richard W.; Parker, Michael H.; Kulp, John L.; Reitz, Allen B.; Ricciardi, Robert P.

doi:10.1016/j.jtos.2020.11.001

Cited by 8 publications

(4 citation statements)

References 29 publications

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“…The biofilms entrenched in STARS bristles were serially diluted and subjected to standard virus plaque assay to evaluate the amount of viable HCoV-OC43 using Vero E6 cells. 48 HCoV-OC43 plaques were quantified at 7 days after infection of Vero E6 cells.…”

Section: Methodsmentioning

confidence: 99%

“…For virus detection, S. mutans single species biofilms were incubated with human coronavirus OC43 (HCoV-OC43) at 5 × 10 5 plaque-forming unit (PFU) mL –1 at 4 °C for 4 h. The biofilms were washed 3 times with phosphate-buffered saline to remove unabsorbed virus and treated with STARS bristles as described above. The biofilms entrenched in STARS bristles were serially diluted and subjected to standard virus plaque assay to evaluate the amount of viable HCoV-OC43 using Vero E6 cells . HCoV-OC43 plaques were quantified at 7 days after infection of Vero E6 cells.…”

Section: Experimental Sectionmentioning

confidence: 99%

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Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth

Babeer

Liu

et al. 2022

ACS Nano

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The eradication of biofilms remains an unresolved challenge across disciplines. Furthermore, in biomedicine, the sampling of spatially heterogeneous biofilms is crucial for accurate pathogen detection and precise treatment of infection. However, current approaches are incapable of removing highly adhesive biostructures from topographically complex surfaces. To meet these needs, we demonstrate magnetic field-directed assembly of nanoparticles into surface topography-adaptive robotic superstructures (STARS) for precision-guided biofilm removal and diagnostic sampling. These structures extend or retract at multilength scales (micro-to-centimeter) to operate on opposing surfaces and rapidly adjust their shape, length, and stiffness to adapt and apply high-shear stress. STARS conform to complex surface topographies by entering angled grooves or extending into narrow crevices and "scrub" adherent biofilm with multiaxis motion while producing antibacterial reagents on-site. Furthermore, as the superstructure disrupts the biofilm, it captures bacterial, fungal, viral, and matrix components, allowing sample retrieval for multiplexed diagnostic analysis. We apply STARS using automated motion patterns to target complex three-dimensional geometries of ex vivo human teeth to retrieve biofilm samples with microscale precision, while providing "toothbrushing-like" and "flossing-like" action with antibacterial activity in real-time to achieve mechanochemical removal and multikingdom pathogen detection. This approach could lead to autonomous, multifunctional antibiofilm platforms to advance current oral care modalities and other fields contending with harmful biofilms on hard-to-reach surfaces.

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Section: Methodsmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth

Babeer

Liu

et al. 2022

ACS Nano

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“…Due to emerging resistance to antiviral medication, there is a need to use other medications that target other viral proteins. This prompted Guan et al [ 186 ] to study the effect of stapled peptides on HSV-1 DNA synthesis and HSV-1 infection[ 186 ].…”

Section: Antiviral Therapy For Herpes Simplex Keratitis: Efficacy And...mentioning

confidence: 99%

Herpes simplex keratitis: A brief clinical overview

Musa,

Enaholo,

Aluyi-Osa

et al. 2024

World J Virol

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The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

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“…This study provides new insights into the determinants of HSV-1 replication and infectivity and provides a framework for the design of drugs that will offer new ways to combat herpesvirus infections with minimal to no side effects. In addition to the use of acyclovir and ganciclovir, nanocarriers, prodrugs, peptide conjugation, and in situ gelling systems have been used to slow the onset or progression of HSK and HSV-1 replication in vitro and in animal models [40,41,[54][55][56][57][58][59][60]. Therefore, these studies and many more have evaluated the antiviral activities of natural or synthesized compounds as potential treatments for viral keratitis.…”

Section: Plos Pathogensmentioning

confidence: 99%

Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo

Wang

Jaggi

et al. 2021

PLoS Pathog

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HSV glycoprotein K (gK) is an essential herpes protein that contributes to enhancement of eye disease. We previously reported that gK binds to signal peptide peptidase (SPP) and that depletion of SPP reduces HSV-1 infectivity in vivo. To determine the therapeutic potential of blocking gK binding to SPP on virus infectivity and pathogenicity, we mapped the gK binding site for SPP to a 15mer peptide within the amino-terminus of gK. This 15mer peptide reduced infectivity of three different virus strains in vitro as determined by plaque assay, FACS, and RT-PCR. Similarly, the 15mer peptide reduced ocular virus replication in both BALB/c and C57BL/6 mice and also reduced levels of latency and exhaustion markers in infected mice when compared with control treated mice. Addition of the gK-15mer peptide also increased the survival of infected mice when compared with control mice. These results suggest that blocking gK binding to SPP using gK peptide may have therapeutic potential in treating HSV-1-associated infection.

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Herpes Simplex Virus-1 infection in human primary corneal epithelial cells is blocked by a stapled peptide that targets processive DNA synthesis

Cited by 8 publications

References 29 publications

Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth

Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth

Herpes simplex keratitis: A brief clinical overview

Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo

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