Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development.
TL;DR: In this paper, the effect of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA was modeled.
Abstract: Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. While gamma (γ) rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modeled the effect of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. Our findings showed that γ rays produced significant spike protein damage, but densely ionizing charged particles induced less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope was sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.
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TL;DR: A comprehensive and systematic methodology-centered narrative about the status of molecular modeling, simulation, and prediction of SARS-CoV-2 is presented in this article, where a review of the literature on molecular modelling, simulation and prediction is presented.
Abstract: The deadly coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gone out of control globally. Despite much effort by scientists, medical experts, and society in general, the slow progress on drug discovery and antibody therapeutic development, the unknown possible side effects of the existing vaccines, and the high transmission rate of the SARS-CoV-2, remind us of the sad reality that our current understanding of the transmission, infectivity, and evolution of SARS-CoV-2 is unfortunately very limited. The major limitation is the lack of mechanistic understanding of viral-host cell interactions, the viral regulation, protein-protein interactions, including antibody-antigen binding, protein-drug binding, host immune response, etc. This limitation will likely haunt the scientific community for a long time and have a devastating consequence in combating COVID-19 and other pathogens. Notably, compared to the long-cycle, highly cost, and safety-demanding molecular-level experiments, the theoretical and computational studies are economical, speedy, and easy to perform. There exists a tsunami of the literature on molecular modeling, simulation, and prediction of SARS-CoV-2 that has become impossible to fully be covered in a review. To provide the reader a quick update about the status of molecular modeling, simulation, and prediction of SARS-CoV-2, we present a comprehensive and systematic methodology-centered narrative in the nick of time. Aspects such as molecular modeling, Monte Carlo (MC) methods, structural bioinformatics, machine learning, deep learning, and mathematical approaches are included in this review. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are assessing the current status in the field.
25 citations
TL;DR: It is proposed here that accelerated heavy ions can be used to inactivate SARS-CoV-2 viruses with small damage to the spike proteins of the envelope and can then provide an intact virion for vaccine development.
Abstract: Virus irradiation has been performed for many decades for basic research studies, sterilization, and vaccine development The COVID-19 outbreak is currently causing an enormous effort worldwide for finding a vaccine against coronavirus High doses of γ-rays can be used for the development of vaccines that exploit inactivated virus This technique has been gradually replaced by more practical methods, in particular the use of chemicals, but irradiation remains a simple and effective method used in some cases The technique employed for inactivating a virus has an impact on its ability to induce an adaptive immune response able to confer effective protection We propose here that accelerated heavy ions can be used to inactivate SARS-CoV-2 viruses with small damage to the spike proteins of the envelope and can then provide an intact virion for vaccine development © Copyright © 2020 Durante, Schulze, Incerti, Francis, Zein and Guzman
19 citations
TL;DR: In the field of radiation biophysics, heavy ions have been used in many biomedical fields, such as treatment of heart arrhythmia or inactivation of viruses for vaccine development as mentioned in this paper.
Abstract: Heavy ions are riveting in radiation biophysics, particularly in the areas of radiotherapy and space radiation protection. Accelerated charged particles can indeed penetrate deeply in the human body to sterilize tumors, exploiting the favorable depth-dose distribution of ions compared to conventional X rays. Conversely, the high biological effectiveness in inducing late effects presents a hazard for manned space exploration. Even after half a century of accelerator-based experiments, clinical applications and flight research, these two topics remain both fascinating and baffling. Heavy-ion therapy is very expensive, and despite the clinical success it remains controversial. Research on late radiation morbidity in spaceflight led to a reduction in uncertainty, but also pointed to new risks previously underestimated, such as possible damage to the central nervous system. Recently, heavy ions have also been used in other, unanticipated biomedical fields, such as treatment of heart arrhythmia or inactivation of viruses for vaccine development. Heavy-ion science nicely merges physics and biology and remains an extraordinary research field for the 21st century.
3 citations
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TL;DR: In this paper, the authors analyzed the properties of magnetic gold nanoparticles in monoenergetic photons and brachytherapy, and investigated whether the magnetic field contributes to the sensitization process.
Abstract: The application of metal nanoparticles as sensitization materials is a common strategy that is used to study dose enhancement in radiotherapy. Recent in vitro tests have revealed that magnetic gold nanoparticles can be used in cancer therapy under a magnetic field to enhance the synergistic efficiency in radiotherapy and photothermal therapy. However, magnetic gold nanoparticles have rarely been studied as sensitization materials. In this study, we obtained further results of the sensitization properties of magnetic gold nanoparticles using the Monte Carlo method TOPAS and TOPAS-nBio. We analyzed the properties of magnetic gold nanoparticles in monoenergetic photons and brachytherapy, and we investigated whether the magnetic field contributes to the sensitization process. Our results demonstrated that the dose enhancement factor of the magnetic gold nanoparticles was 16.7% lower than that of gold nanoparticles in a single particle irradiated by monoenergetic photons. In the cell model, the difference was less than 8.1% in the cytoplasm. We revealed that the magnetic field has no detrimental effect on radiosensitization. Moreover, the sensitization properties of magnetic gold nanoparticles in a clinical brachytherapy source have been revealed for the first time.
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TL;DR: In this article, an ionic lens is integrated onto the NEMS chip to focus the analytes towards an open window aligned with the active area of the NEM electrostatically, and the mass spectrum of SARS-CoV-2 and BoHV-1 virions is obtained.
Abstract: Mass spectrometry of intact nanoparticles and viruses can serve as a unique characterization tool for material science and biophysics. Inaccessible by conventional techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by NEMS (Nano-electromechanical Systems) based Mass Spectrometry, where charged and isolated analyte particles are generated by Electrospray Ionization (ESI) in air and transported onto the NEMS surface for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes towards the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ionic lens onto the NEMS chip. The ionic lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes towards an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with record capture efficiencies. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup and the operation capability under ambient conditions, the technique brings NEMS mass spectrometry one step closer towards efficient mass detection of engineered nanoparticles and biological samples.
References
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University of Genoa1, University of Manchester2, KEK3, CERN4, Imperial College London5, Stanford University6, Tata Institute of Fundamental Research7, Istituto Nazionale di Fisica Nucleare8, University of Pittsburgh9, Lyon College10, TRIUMF11, Northeastern University12, Thomas Jefferson National Accelerator Facility13, University of Córdoba (Spain)14, Goethe University Frankfurt15, University of Southampton16, University of Udine17, University of Alberta18, Tokyo Metropolitan University19, Helsinki Institute of Physics20, National Research Nuclear University MEPhI21, University of Bath22, Niigata University23, Naruto University of Education24, Kobe University25, University of Calabria26, University of Trieste27, European Space Agency28, University of Birmingham29, Ritsumeikan University30, Qinetiq31, École Polytechnique Fédérale de Lausanne32, Massachusetts Institute of Technology33, Brookhaven National Laboratory34
01 Jul 2003-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The Gelfant 4 toolkit as discussed by the authors is a toolkit for simulating the passage of particles through matter, including a complete range of functionality including tracking, geometry, physics models and hits.
Abstract: G eant 4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics.
18,904 citations
TL;DR: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older and safety over a median of 2 months was similar to that of other viral vaccines.
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...
10,274 citations
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
9,231 citations
University of Manchester1, KEK2, CERN3, Imperial College London4, University of Cantabria5, Stanford University6, Northeastern University7, TRIUMF8, Helsinki Institute of Physics9, Kobe University10, Spanish National Research Council11, Karolinska Institutet12, Qinetiq13, Naruto University of Education14, European Space Agency15, Ritsumeikan University16, University of California, Santa Cruz17
TL;DR: GeGeant4 as mentioned in this paper is a software toolkit for the simulation of the passage of particles through matter, it is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection.
Abstract: Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Its functionality and modeling capabilities continue to be extended, while its performance is enhanced. An overview of recent developments in diverse areas of the toolkit is presented. These include performance optimization for complex setups; improvements for the propagation in fields; new options for event biasing; and additions and improvements in geometry, physics processes and interactive capabilities
6,063 citations
University of Oxford1, Federal University of São Paulo2, University of the Witwatersrand3, Stellenbosch University4, Liverpool School of Tropical Medicine5, University of Sheffield6, University of London7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University Hospital Southampton NHS Foundation Trust9, University Hospitals Bristol NHS Foundation Trust10, Guy's and St Thomas' NHS Foundation Trust11, University Hospitals Birmingham NHS Foundation Trust12, St George's, University of London13, AstraZeneca14, North Bristol NHS Trust15, University College Hospital16, University of Hull17, Escola Bahiana de Medicina e Saúde Pública18, Federal University of Rio Grande do Norte19, Northwest University (China)20, Universidade Federal de Santa Maria21, Glasgow Dental Hospital and School22, Boston Children's Hospital23, Universidade Federal do Rio Grande do Sul24, Western General Hospital25, University of Glasgow26, Cambridge University Hospitals NHS Foundation Trust27, University of Cambridge28, Nottingham University Hospitals NHS Trust29, Aneurin Bevan University Health Board30
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
3,741 citations