title: Butyroyl-arginine as a potent virus inactivation agent.
abstract: Virus inactivation is a critical step in the manufacturing of recombinant therapeutic proteins, in particular antibodies, using mammalian expression systems. We have shown in the previous paper that arginine is effective in inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus at low temperature under mildly acidic pH, i.e., above pH 4.0; above this pH, conformational changes of most antibodies are negligible. We have here extended virus inactivation study of arginine to other enveloped viruses, such as Sendai virus and Newcastle Disease Virus (NDV), and observed that arginine was ineffective against both viruses under the similar conditions, i.e., on ice and above pH 4.0. However, an arginine derivative, butyroyl-arginine, showed a strong virucidal potency against Sendai virus, leading to a 4log reduction in virus yield at pH 4.0, but not against NDV. In addition, although arginine and butyroyl-arginine were equally effective against influenza virus having a cleaved form of hemagglutinin spike proteins, only butyroyl-arginine was significantly effective against the same virus, but having an uncleaved hemagglutinin spike proteins. Furthermore, butyroyl-arginine was more effective than arginine against HSV-1 at pH 4.5; i.e., it has a broader pH spectrum than does arginine.
authors.affiliation: Division of Virology, Department of Cellular and Molecular Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Tsujimoto
authors.forename: A Hajime
authors.initials: AH
authors.lastname: Koyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ejima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007668:Kidney; D009522:Newcastle disease virus / Q000187:drug effects; D029082:Sendai virus / Q000187:drug effects; D013696:Temperature; D014709:Vero Cells; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C532211:butyroyl-arginine; D001120:Arginine