title: Solvent-induced virus inactivation by acidic arginine solution.
abstract: Viral clearance is a primary concern for parenteral protein biopharmaceuticals. Low pH, detergent/solvent wash, or heating, called pasteurization, has been the main process for virus inactivation. Detergent/solvent wash is also used to treat superficial infectious diseases, including herpes simplex virus (HSV) infections. Herein we examined virus inactivation effects of acidic arginine on HSV type 2 (HSV-2) as a function of pH and temperature in an attempt to find solvent conditions that are effective for virus inactivation, yet are compatible with in vivo applications. Aqueous arginine at 0.7 M was highly effective on HSV-2, more so at lower pH and higher temperature. Its effects were stronger than 0.1 M citrate, 0.1 M citrate/0.6 M NaCl or 0.7 M citrate at any pH and temperature. This demonstrates that strong virus inactivation effects of arginine are not simply due to ionic strength or high concentration and arginine possesses a unique property that results in irreversible damage in virus particles. Such strong virus inactivation effects can be used in vivo for certain superficial infectious diseases, such as genital infections.
authors.affiliation: Division of Virology, Department of Cellular and Molecular Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Tsujimoto
authors.forename: Misao
authors.initials: M
authors.lastname: Uozaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
authors.forename: A Hajime
authors.initials: AH
authors.lastname: Koyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D012996:Solutions / Q000737:chemistry / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology*; D013696:Temperature; D014709:Vero Cells; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012996:Solutions; D012997:Solvents; D001120:Arginine