Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development

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 (c) 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 c 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.

Inactivation of SARS-CoV-2 by charged particles for Future Vaccine Production Applications: A Monte Carlo study

“…The survival curves indicate that high-LET radiations require a larger dose to inactivate SARS-CoV-2. This is consistent with the results of the previous study by Francis et al (2021) , however, the data are not quantitatively the same. This may be due to differences in geometry of SARS-CoV-2.…”

“…Therefore, the number of damaged spikes normalized per single RNA damage is interesting. We are looking for a radiation field that causes the least number of damaged spikes per single RNA break as suggested by ( Durante et al, 2020 ; Francis et al, 2021 ) for the first time. This ratio is represented in Fig.…”

“…Villagomez-Bernabe et al simulated the SARS-CoV-2 structure with TOPAS Monte Carlo code, and investigated the effect of the 3D arrangement of the Ribonucleic acid (RNA) on survival curves ( Villagomez-Bernabe et al, 2020 ). In a comprehensive study, Francis et al simulated the SARS-CoV-2 inactivation caused by photons, electrons, and heavy ions using Geant4-DNA Monte Carlo code ( Francis et al, 2021 ). They concluded that by considering the same damage to the RNA, densely ionizing or high-linear-energy-transfer (LET) radiation would be more advantageous in vaccine development due to their less damage to the spike proteins than that of sparsely ionizing (low-LET) radiation.…”

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…An MC simulation of ionizing radiation damage to the SARS-CoV-2 found that γ-rays produced significant S protein damage but much less membrane damage. 199 Thus, the γ-rays were proposed as a new effective tool to develop inactivated vaccines. A metropolis MC sampling process was applied to simulate a pharmacokinetic model of the human immunodeficiency virus (HIV) drug darunavir against SARS-CoV-2.…”

Monte Carlo Prediksi Tingkat Prevalensi Stunting Kabupaten Lima Puluh Kota Menggunakan Metode Monte Carlo

“…Simulasi adalah suatu metode yang digunakan untuk mengeksekusi perilaku dan model dalam perangkat lunak [3]. Model simulasi biasanya memperhitungkan keadaan sistem yang ditangkap melalui nilainilai variabel yang telah ditetapkan [4]. Simulasi sering digunakan dalam mempelajari atau menganalisis perilaku kerja dari suatu sistem atau proses oleh manajemen dalam menyelesaikan pekerjaannya [5].…”