Physiochemical properties of enveloped viruses and arginine dictate inactivation. Issue 7 (13th May 2021)

• Record Type: Journal Article
• Authors: Meingast, Christa L.; Joshi, Pratik U.; Turpeinen, Dylan G.; Xu, Xuankuo; Holstein, Melissa; Feroz, Hasin; Ranjan, Swarnim; Ghose, Sanchayita; Li, Zheng Jian; Heldt, Caryn L.
• Is Part Of: Biotechnology journal. Volume 16:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-13
• Subjects: arginine -- herpes simplex virus -- hydrophobicity -- lipid bilayer -- pseudorabies virus; Biotechnology -- Periodicals; 660.605
• DOI: 10.1002/biot.202000342
• Languages: English
• ISSNs: 1860-6768

Abstract

Abstract: Background: Therapeutic protein manufacturing would benefit by having an arsenal of ways to inactivate viruses. There have been many publications on the virus inactivation ability of arginine at pH 4.0, but the mechanism of this inactivation is unknown. This study explored how virus structure and solution conditions enhance virus inactivation by arginine and leads to a better understanding of the mechanism of virus inactivation by arginine. Results: Large diameter viruses from the Herpesviridae family (SuHV‐1, HSV‐1) with loosely packed lipids were highly inactivated by arginine, whereas small diameter, enveloped viruses (equine arteritis virus (EAV) and bovine viral diarrhea virus (BVDV)) with tightly packed lipids were negligibly inactivated by arginine. To increase the inactivation of viruses resistant to arginine, arginine‐derivatives and arginine peptides were tested. Derivates and peptides demonstrated that a greater capacity for clustering and added hydrophobicity enhanced virus inactivation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) detected increases in virus size after arginine exposure, supporting the mechanism of lipid expansion. Conclusions: Arginine most likely interacts with the lipid membrane to cause inactivation. This is shown by larger viruses being more sensitive to inactivation and expansion of the viral size. The enhancement of arginine inactivation when increased hydrophobic molecules are present or arginine is clustered demonstrates a potential mechanism of how arginine interacts with the lipid membrane. Abstract : Virus structure and solution conditions greatly contribute to the inactivation of virus by arginine. Virus inactivation at pH 4 is dependent on size, with larger viruses having more inactivation. Clustering of arginine and added hydrophobicity increased the inactivation of smaller viruses. Results indicate that the interaction of arginine with the viral envelope is the most likely mechanism of virus inactivation.