MOPS and coxsackievirus B3 stability

Abstract

Study of coxsackievirus B3 strain 28 (CVB3/28) stability using MOPS to improve buffering in the experimental medium revealed that MOPS (3-morpholinopropane-1-sulfonic acid) increased CVB3 stability and the effect was concentration dependent. Over the pH range 7.0 to 7.5, virus stability was affected by both pH and MOPS concentration. Computer-simulated molecular docking showed that MOPS can occupy the hydrophobic pocket in capsid protein VP1 where the sulfonic acid head group can form ionic and hydrogen bonds with Arg95 and Asn211 near the pocket opening. The effects of MOPS and hydrogen ion concentrations on the rate of virus decay were modeled by including corresponding parameters in a recent kinetic model. These results indicate that MOPS can directly associate with CVB3 and stabilize the virus, possibly by altering capsid conformational dynamics.

Albumin Enhances the Rate at Which Coxsackievirus B3 Strain 28 Converts to A-Particles

“…Derivations of the equations to fit previous and revised models were as follows (25,26). The current working model for CVB3 breathing and conversion to A-particles in the absence of a receptor is…”

“…The model(s) when MOPS is present is as follows. The previous model for MOPS stabilization of CVB3/28 was based on MOPS binding to the virus, possibly in the VP1 pocket (26).…”

“…The discovery that serum destabilizes CVB3/28 necessitates refinement of our working model for receptor-catalyzed conversion to A-particles to account for the destabilized virus (25,26). The experiments that supported that model were all done in DMEM-10 (8.9% FBS) using CVB3/28 (17,26). There is almost certainly an ensemble of virus conformations between the closed state and the open state that precedes the A-particle.…”

“…The finding that albumin destabilizes CVB3/28 requires reconsideration of mechanisms by which MOPS (morpholinepropanesulfonic acid) might stabilize CVB3/28 (26). The original model involved MOPS binding to virus, possibly in the VP1 pocket.…”

“…Now, it is possible that MOPS binds albumin, rather than virus, and interferes with its ability to destabilize CVB3/28 (29). The MOPS models were written by adding MOPS (M) and the virus closed conformation (V) in equilibrium with the virus-MOPS complex (VM), or MOPS and BSA (B) in equilibrium with MOPS bound to BSA (MB) to equation 4, to give equation 16 or 18 (see Materials and Methods), respectively, and analyzed by testing the resulting solutions for k app against the data from the work of Carson et al (26). In…”