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Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development
Ziad Francis1, Sebastien Incerti2, Sara A Zein2
1Saint Joseph University, U.R. Mathématiques et Modélisation, Beirut, Lebanon.
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.
Insights
Accelerated charged particles may be a superior method for inactivating SARS-CoV-2 for vaccine development. This approach minimizes damage to viral proteins, potentially enhancing vaccine efficacy against enveloped viruses.
Area of Science:
- Virology
- Radiation Biology
- Vaccine Development
Background:
- Inactivated virus vaccines are a strategy for SARS-CoV-2 vaccine development.
- Ionizing radiation, like gamma (γ) rays, inactivates viruses by damaging nucleic acids but can also damage viral envelope proteins, potentially affecting immunogenicity.
- Damage to viral envelope proteins may compromise the ability to induce a protective immune response.
Purpose of the Study:
- To model the effects of sparsely and densely ionizing radiation on SARS-CoV-2.
- To compare the damage induced by different types of radiation on viral RNA and proteins.
- To evaluate the potential of different radiation types for developing effective SARS-CoV-2 vaccines.
Main Methods:
- Utilized the Monte Carlo toolkit Geant4-DNA for simulations.
- Employed a realistic 3D model of the SARS-CoV-2 virus.
- Calculated the number of lesions induced in viral RNA, spike proteins, and membrane proteins by different radiation types.
Main Results:
- Gamma (γ) rays caused significant damage to spike proteins.
- Densely ionizing charged particles induced fewer membrane protein lesions compared to gamma rays for equivalent RNA damage.
- A single traversal of a charged particle was sufficient to inactivate the virus.
Conclusions:
- Accelerated charged particles offer a method for virus inactivation with reduced structural damage to envelope proteins.
- This approach may preserve the antigenic properties of viral proteins, enhancing vaccine immunogenicity.
- Charged particle irradiation represents a promising tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.
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