Abstract

Enteroviruses are common agents of infectious disease that are spread by the fecal-oral route. They are readily inactivated by mild heat, which causes the viral capsid to disintegrate or undergo conformational change. While beneficial for the thermal treatment of food or water, this heat sensitivity poses challenges for the stability of enterovirus vaccines. The thermostability of an enterovirus can be modulated by the composition of the suspending matrix, though the effects of the matrix on virus stability are not understood. Here we determined the thermostability of four enterovirus strains in solutions with varying concentrations of NaCl, and pH. The experimental findings were combined with molecular modeling of the protein interaction forces at the pentamer and the protomer interfaces of the viral capsids. While pH only affected thermostability, increasing NaCl concentrations raised the breakpoint temperature of all viruses tested by up to 20 °C. This breakpoint shift could be explained by an enhancement of the van der Waals attraction forces at the two protein interfaces. In comparison, the (net repulsive) electrostatic interactions were less affected by NaCl. Depending on the interface considered, the breakpoint temperature shifted by 7.5 or 5.6 °C per 100 kcal/(mol*Å) increase in protein interaction force.

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