Virus Isoelectric Point Estimation: Theories and Methods

Abstract

Much of virus fate, both in the environment and physical/chemical treatment, is dependent on electrostatic interactions. Developing an accurate means of predicting virion isoelectric point (pI) would help to understand and anticipate virus fate and transport, especially for viruses that are not readily propagated in the lab. One simple approach to predicting pI estimates the pH at which the sum of charges from ionizable amino acids in capsid proteins approaches zero. However, predicted pIs based on capsid charges frequently deviate by several pH units from empirically measured pIs. Recently, the discrepancy between empirical and predicted pI was attributed to the electrostatic neutralization of predictable polynucleotide-binding regions (PBRs) of the capsid interior. In this paper, we review models presupposing the A) influence of the viral polynucleotide on surface charge, or B) contribution of only exterior residues to surface charge. We then compare these models to the approach of excluding only PBRs and hypothesize a conceptual electrostatic model that aligns with this approach. The PBR exclusion method outperformed methods based on 3D structure and accounted for major discrepancies in predicted pIs without adversely affecting pI prediction for a diverse range of viruses. In addition, the PBR exclusion method was determined to be the best available method for predicting virus pI since: A) PBRs are predicted independently of the impact on pI, B) PBR prediction relies on proteome sequences rather than detailed structural models, and C) PBR exclusion was successfully demonstrated on a diverse set of viruses. These models apply to nonenveloped viruses only. A similar model for enveloped viruses is complicated by lack of data on enveloped virus pI, as well as uncertainties regarding the influence of the phospholipid envelope on charge and ion gradients.

Effects of surface charge and environmental factors on the electrostatic interaction of fiber with virus-like particle: A case of coronavirus

“…In our calculation, the DNA/RNA core and its viral lipid envelope are electrically screened, and only S proteins are responsible for the electrostatic interaction. These assumptions are consistent with a prior work 40 . For S proteins, their shape and charge as described in Fig.…”

Effects of surface charge and environmental factors on the electrostatic interaction of fiber with virus-like particle: A case of coronavirus

“…These assumptions are consistent with a prior work. 40 For S proteins, their shape and charge as described in Fig. 1 can be extracted from the Protein Data Bank entry PDB: 6VXX.…”

Adherence of SARS-CoV-2 delta variant to surgical mask and N95 respirators

“…This protein looks to have a particular disorder [16] probably because of its interaction with the membrane proteins [17]. Thus, the electrostatic interaction of the virus and the electret is based on the charge of the Spike protein [18]. One of the main variables regarding the isoelectric point of the Spike protein is the large number of ionizable amino acids that contribute to the net charge (e.g., C, D, E, H, K, R, and Y) [15].…”