Exploring Non-Alcohol-Based Disinfectant: Virucidal Efficacy of Arginine and Zinc Chloride Against Feline CalicivirusAn Approach to Safer Disinfection: Exploring the Virucidal Efficacy of Arginine and Zinc Chloride Against

Marcella Kong Li Ying ¹ Srdan Masirevic ² Yong Wah Tan ³ Jan K. Marzinek ² StephenJohn Fox ¹ Chandra S Verma ² Peter J Bond ^2,4 Yoshiki Ishida ¹ Jiquan Liu ¹ Chun Song Chua ¹ Justin Jang Hann Chu ^3,5,6*

• ¹ Procter & Gamble (Singapore), Singapore, Singapore
• ² Bioinformatics Institute, Agency for Science, Technology and Research, Singapore, Singapore
• ³ Collaborative Translation Unit for HFMD, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, Singapore
• ⁴ Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore
• ⁵ Infectious Disease Translation Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Singapore, Singapore
• ⁶ Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Singapore

Norovirus, a leading cause of acute gastroenteritis worldwide, is notably stable in the environment due to its non-enveloped nature. In the absence of effective vaccines or treatments, disinfection remains the primary prevention strategy, highlighting the importance of virucidal efficacy in household care products. Conventional effective disinfectants are predominantly alcohol-based, but alcohol is known to pose health risks, such as skin irritation. This study investigates a non-alcohol-based alternative, specifically a combination of Arginine and Zinc chloride (ZnCl2). Traditional disinfectants, while effective, often rely on harsh chemicals that pose health risks, prompting the search for safer alternatives. This study explores the use of a non-alcohol-based solution, specifically a combination of Arginine and Zinc chloride (ZnCl2), as a safer alternative. Utilizing MS2 bacteriophage as a surrogate, we identified a robust combination of arginine and ZnCl2 that is effective against Feline Calicivirus (FCV), a mammalian virus surrogate model for Norovirus. Our results determined a 5 minute contact time at pH 11 as optimal, achieving significant virucidal activity against FCV without pH-induced reversibility. Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM) analyses suggested that the mechanism of action for the Arg-Zn 2+ -Arg complex does not involve capsid disruption. Further insights from molecular modelling studies revealed that the complex potentially inhibits FCV by occupying a key capsid binding pocket essential for Junctional Adhesion Molecule (JAM) receptor engagement, thereby preventing viral entry. These findings allow us to propose a novel and non-alcohol-based safer virucidal approach against viruses from the Caliciviridae family, highlighting the potential of Arg-Zn 2+ -Arg complexes in public health protection.