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13 pages, 1986 KiB

Open AccessArticle

Nano-Biomechanical Investigation of Phosphatidylserine-Mediated Ebola Viral Attachment via Human Gas6 and Axl

by Decheng Hou, Qian Mu, Weixuan Chen, Wenpeng Cao and Xiaohui Frank Zhang

Viruses 2024, 16(11), 1700; https://doi.org/10.3390/v16111700 - 30 Oct 2024

Viewed by 869

Abstract

The Ebola virus is a deadly pathogen that has been threatening public health for decades. Recent studies have revealed alternative viral invasion routes where Ebola virus approaches cells via interactions among phosphatidylserine (PS), PS binding ligands such as Gas6, and TAM family receptors [...] Read more.

The Ebola virus is a deadly pathogen that has been threatening public health for decades. Recent studies have revealed alternative viral invasion routes where Ebola virus approaches cells via interactions among phosphatidylserine (PS), PS binding ligands such as Gas6, and TAM family receptors such as Axl. In this study, we investigate the interactions among phosphatidylserine on the Ebola viral-like particle (VLP) membrane, human Gas6, and human Axl using atomic force microscope-based single molecule force spectroscopy to compare their binding strength and affinity from a biomechanical perspective. The impact of calcium ions on their interactions is also studied and quantified to provide more details on the calcium-dependent phosphatidylserine-Gas6 binding mechanism. Our results indicate that, in the presence of calcium ions, the binding strengths of VLP-Gas6 and VLP-Gas6-Axl increase but are still weaker than that of Gas6-Axl, and the binding affinity of VLP-Gas6 and VLP-Gas6-Axl is largely improved. The binding strength and affinity of Gas6-Axl basically remain the same, indicating no impact in the presence of calcium ions. Together, our study suggests that, under physiological conditions with calcium present, the Ebola virus can utilize its membrane phosphatidylserine to dock on cell surface via Gas6-Axl bound complex. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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16 pages, 2116 KiB

Open AccessArticle

An Engineered M13 Filamentous Nanoparticle as an Antigen Carrier for a Malignant Melanoma Immunotherapeutic Strategy

by Nuša Brišar, Katja Šuster, Simona Kranjc Brezar, Robert Vidmar, Marko Fonović and Andrej Cör

Viruses 2024, 16(2), 232; https://doi.org/10.3390/v16020232 - 1 Feb 2024

Cited by 2 | Viewed by 1838

Abstract

Bacteriophages, prokaryotic viruses, hold great potential in genetic engineering to open up new avenues for vaccine development. Our study aimed to establish engineered M13 bacteriophages expressing MAGE-A1 tumor peptides as a vaccine for melanoma treatment. Through in vivo experiments, we sought to assess [...] Read more.

Bacteriophages, prokaryotic viruses, hold great potential in genetic engineering to open up new avenues for vaccine development. Our study aimed to establish engineered M13 bacteriophages expressing MAGE-A1 tumor peptides as a vaccine for melanoma treatment. Through in vivo experiments, we sought to assess their ability to induce robust immune responses. Using phage display technology, we engineered two M13 bacteriophages expressing MAGE-A1 peptides as fusion proteins with either pVIII or pIIII coat proteins. Mice were intraperitoneally vaccinated three times, two weeks apart, using two different engineered bacteriophages; control groups received a wild-type bacteriophage. Serum samples taken seven days after each vaccination were analyzed by ELISA assay, while splenocytes harvested seven days following the second boost were evaluated by ex vivo cytotoxicity assay. Fusion proteins were confirmed by Western blot and nano-LC-MS/MS. The application of bacteriophages was safe, with no adverse effects on mice. Engineered bacteriophages effectively triggered immune responses, leading to increased levels of anti-MAGE-A1 antibodies in proportion to the administered bacteriophage dosage. Anti-MAGE-A1 antibodies also exhibited a binding capability to B16F10 tumor cells in vitro, as opposed to control samples. Splenocytes demonstrated enhanced CTL cytotoxicity against B16F10 cells. We have demonstrated the immunogenic capabilities of engineered M13 bacteriophages, emphasizing their potential for melanoma immunotherapy. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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15 pages, 2996 KiB

Open AccessArticle

Dramatic Differences between the Structural Susceptibility of the S1 Pre- and S2 Postfusion States of the SARS-CoV-2 Spike Protein to External Electric Fields Revealed by Molecular Dynamics Simulations

by Alexander Lipskij, Claudia Arbeitman, Pablo Rojas, Pedro Ojeda-May and Martin E. Garcia

Viruses 2023, 15(12), 2405; https://doi.org/10.3390/v15122405 - 11 Dec 2023

Cited by 1 | Viewed by 1790

Abstract

In its prefusion state, the SARS-CoV-2 spike protein (similarly to other class I viral fusion proteins) is metastable, which is considered to be an important feature for optimizing or regulating its functions. After the binding process of its S1 subunit (S1) with ACE2, [...] Read more.

In its prefusion state, the SARS-CoV-2 spike protein (similarly to other class I viral fusion proteins) is metastable, which is considered to be an important feature for optimizing or regulating its functions. After the binding process of its S1 subunit (S1) with ACE2, the spike protein (S) undergoes a dramatic conformational change where S1 splits from the S2 subunit, which then penetrates the membrane of the host cell, promoting the fusion of the viral and cell membranes. This results in the infection of the host cell. In a previous work, we showed—using large-scale molecular dynamics simulations—that the application of external electric fields (EFs) induces drastic changes and damage in the receptor-binding domain (RBD) of the wild-type spike protein, as well of the Alpha, Beta, and Gamma variants, leaving a structure which cannot be recognized anymore by ACE2. In this work, we first extend the study to the Delta and Omicron variants and confirm the high sensitivity and extreme vulnerability of the RBD of the prefusion state of S to moderate EF (as weak as 10⁴ V/m), but, more importantly, we also show that, in contrast, the S2 subunit of the postfusion state of the spike protein does not suffer structural damage even if electric field intensities four orders of magnitude higher are applied. These results provide a solid scientific basis to confirm the connection between the prefusion-state metastability of the SARS-CoV-2 spike protein and its susceptibility to be damaged by EF. After the virus docks to the ACE2 receptor, the stable and robust postfusion conformation develops, which exhibits a similar resistance to EF (damage threshold higher than 10⁸ V/m) like most globular proteins. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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17 pages, 11223 KiB

Open AccessArticle

Neutralizing Efficacy of Encapsulin Nanoparticles against SARS-CoV2 Variants of Concern

by Sara Khaleeq, Nayanika Sengupta, Sahil Kumar, Unnatiben Rajeshbhai Patel, Raju S. Rajmani, Poorvi Reddy, Suman Pandey, Randhir Singh, Somnath Dutta, Rajesh P. Ringe and Raghavan Varadarajan

Viruses 2023, 15(2), 346; https://doi.org/10.3390/v15020346 - 25 Jan 2023

Cited by 9 | Viewed by 3989

Abstract

Rapid emergence of the SARS-CoV-2 variants has dampened the protective efficacy of existing authorized vaccines. Nanoparticle platforms offer a means to improve vaccine immunogenicity by presenting multiple copies of desired antigens in a repetitive manner which closely mimics natural infection. We have applied [...] Read more.

Rapid emergence of the SARS-CoV-2 variants has dampened the protective efficacy of existing authorized vaccines. Nanoparticle platforms offer a means to improve vaccine immunogenicity by presenting multiple copies of desired antigens in a repetitive manner which closely mimics natural infection. We have applied nanoparticle display combined with the SpyTag–SpyCatcher system to design encapsulin–mRBD, a nanoparticle vaccine displaying 180 copies of the monomeric SARS-CoV-2 spike receptor-binding domain (RBD). Here we show that encapsulin–mRBD is strongly antigenic and thermotolerant for long durations. After two immunizations, squalene-in-water emulsion (SWE)-adjuvanted encapsulin–mRBD in mice induces potent and comparable neutralizing antibody titers of 10⁵ against wild-type (B.1), alpha, beta, and delta variants of concern. Sera also neutralizes the recent Omicron with appreciable neutralization titers, and significant neutralization is observed even after a single immunization. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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17 pages, 1382 KiB

Open AccessArticle

Novel RT-PCR Using Sugar Chain-Immobilized Gold-Nanoparticles Correlates Patients’ Symptoms: The Follow-Up Study of COVID-19 Hospitalized Patients

by Takashi Kajiya, Hayate Sawayama, Eriko Arima, Mika Okamoto, Masanori Baba, Masaaki Toyama, Kosuke Okuya, Makoto Ozawa, Nobuhiko Atsuchi, Junichiro Nishi and Yasuo Suda

Viruses 2022, 14(11), 2577; https://doi.org/10.3390/v14112577 - 21 Nov 2022

Cited by 1 | Viewed by 2262

Abstract

Background: The transmissible capacity and toxicity of SARS-CoV-2 variants are continually changing. We report here the follow-up study of hospitalized COVID-19 patients from 2020 to 2022. It is known that the PCR diagnosis for hospitalized patients sometimes causes confusion because of the incompatibility [...] Read more.

Background: The transmissible capacity and toxicity of SARS-CoV-2 variants are continually changing. We report here the follow-up study of hospitalized COVID-19 patients from 2020 to 2022. It is known that the PCR diagnosis for hospitalized patients sometimes causes confusion because of the incompatibility between their diagnosis and symptoms. We applied our sugar chain-immobilized gold-nanoparticles for the extraction and partial purification of RNA from specimens for quantitative RT-PCR assay and evaluated whether the results correlate with patients’ symptoms. Methods and Results: Saliva specimens were taken from hospitalized patients with mild or moderate symptoms every early morning. At the time of RT-PCR diagnosis, two methods for the extraction and partial purification of RNA from the specimen were performed: a commonly used Boom (Qiagen) method and our original sugar chain-immobilized gold nanoparticle (SGNP) method. For symptoms, body temperature and oxygen saturation (SpO₂) of patients were monitored every 4 h. Conclusions: It was clear that patients infected with the Delta variant needed more time to recover than those with the Omicron variant, and that the SGNP method showed more realistic correlation with the symptoms of patients compared with the common Qiagen method. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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Review

Jump to: Research

24 pages, 1863 KiB

Open AccessReview

Protein Nanoparticles as Vaccine Platforms for Human and Zoonotic Viruses

by Kush K. Pandey, Bikash R. Sahoo and Asit K. Pattnaik

Viruses 2024, 16(6), 936; https://doi.org/10.3390/v16060936 - 9 Jun 2024

Cited by 2 | Viewed by 2293

Abstract

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. [...] Read more.

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterisation of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs, have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from human viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious viral diseases and enhancing vaccine efficacy and safety. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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14 pages, 1014 KiB

Open AccessReview

Passive Sampler Technology for Viral Detection in Wastewater-Based Surveillance: Current State and Nanomaterial Opportunities

by Alberto Aguayo-Acosta, Mildred G. Jiménez-Rodríguez, Fernando Silva-Lance, Mariel Araceli Oyervides-Muñoz, Arnoldo Armenta-Castro, Orlado de la Rosa, Antonio Ovalle-Carcaño, Elda M. Melchor-Martínez, Zahra Aghalari, Roberto Parra-Saldívar and Juan Eduardo Sosa-Hernández

Viruses 2023, 15(9), 1941; https://doi.org/10.3390/v15091941 - 16 Sep 2023

Cited by 5 | Viewed by 2043

Abstract

Although wastewater-based surveillance (WBS) is an efficient community-wide surveillance tool, its implementation for pathogen surveillance remains limited by ineffective sample treatment procedures, as the complex composition of wastewater often interferes with biomarker recovery. Moreover, current sampling protocols based on grab samples are susceptible [...] Read more.

Although wastewater-based surveillance (WBS) is an efficient community-wide surveillance tool, its implementation for pathogen surveillance remains limited by ineffective sample treatment procedures, as the complex composition of wastewater often interferes with biomarker recovery. Moreover, current sampling protocols based on grab samples are susceptible to fluctuant biomarker concentrations and may increase operative costs, often rendering such systems inaccessible to communities in low-to-middle-income countries (LMICs). As a response, passive samplers have emerged as a way to make wastewater sampling more efficient and obtain more reliable, consistent data. Therefore, this study aims to review recent developments in passive sampling technologies to provide researchers with the tools to develop novel passive sampling strategies. Although promising advances in the development of nanostructured passive samplers have been reported, optimization remains a significant area of opportunity for researchers in the area, as methods for flexible, robust adsorption and recovery of viral genetic materials would greatly improve the efficacy of WBS systems while making them more accessible for communities worldwide. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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56 pages, 12276 KiB

Open AccessReview

Advances in Antiviral Delivery Systems and Chitosan-Based Polymeric and Nanoparticulate Antivirals and Antiviral Carriers

by Dominika Žigrayová, Veronika Mikušová and Peter Mikuš

Viruses 2023, 15(3), 647; https://doi.org/10.3390/v15030647 - 28 Feb 2023

Cited by 20 | Viewed by 4825

Abstract

Current antiviral therapy research is focused on developing dosage forms that enable highly effective drug delivery, providing a selective effect in the organism, lower risk of adverse effects, a lower dose of active pharmaceutical ingredients, and minimal toxicity. In this article, antiviral drugs [...] Read more.

Current antiviral therapy research is focused on developing dosage forms that enable highly effective drug delivery, providing a selective effect in the organism, lower risk of adverse effects, a lower dose of active pharmaceutical ingredients, and minimal toxicity. In this article, antiviral drugs and the mechanisms of their action are summarized at the beginning as a prerequisite background to develop relevant drug delivery/carrier systems for them, classified and briefly discussed subsequently. Many of the recent studies aim at different types of synthetic, semisynthetic, and natural polymers serving as a favorable matrix for the antiviral drug carrier. Besides a wider view of different antiviral delivery systems, this review focuses on advances in antiviral drug delivery systems based on chitosan (CS) and derivatized CS carriers. CS and its derivatives are evaluated concerning methods of their preparation, their basic characteristics and properties, approaches to the incorporation of an antiviral drug in the CS polymer as well as CS nanoparticulate systems, and their recent biomedical applications in the context of actual antiviral therapy. The degree of development (i.e., research study, in vitro/ex vivo/in vivo preclinical testing), as well as benefits and limitations of CS polymer and CS nanoparticulate drug delivery systems, are reported for particular viral diseases and corresponding antivirotics. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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15 pages, 916 KiB

Open AccessReview

Biomimetic Nanotechnology for SARS-CoV-2 Treatment

by Shuo Li, Xue Liu, Gang Liu and Chao Liu

Viruses 2023, 15(3), 596; https://doi.org/10.3390/v15030596 - 21 Feb 2023

Cited by 7 | Viewed by 2933

Abstract

More than 600 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the pandemic of coronavirus disease 2019 (COVID-19). In particular, new waves of COVID-19 caused by emerging SARS-CoV-2 variants pose new health risks to the [...] Read more.

More than 600 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the pandemic of coronavirus disease 2019 (COVID-19). In particular, new waves of COVID-19 caused by emerging SARS-CoV-2 variants pose new health risks to the global population. Nanotechnology has developed excellent solutions to combat the virus pandemic, such as ACE2-based nanodecoys, nanobodies, nanovaccines, and drug nanocarriers. Lessons learned and strategies developed during this battle against SARS-CoV-2 variants may also serve as inspiration for developing nanotechnology-based strategies to combat other global infectious diseases and their variants in the future. Full article

(This article belongs to the Special Issue Nanotechnological Applications in Virology 2023)

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