  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. Although gamma-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 modelled
the impact 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. We show that gamma-rays produce significant spike
protein damage, but densely ionizing charged particles induce less membrane
damage for the same level of RNA lesions, because a single ion traversal
through the nuclear envelope is 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.
