Carboxymethyl-starch:iodine complexes as virucidal agents: salivary amylase triggers on-site iodine release, preventing human coronavirus OC43 replication.

Coronavirus disease 19 (COVID-19), caused by the highly transmissible and pathogenic SARS-CoV-2 virus, has led the global pandemia. While various vaccines have been developed, drugs against SARS-CoV-2 have been primarily focused on repurposing existing antivirals/antimicrobials. In addition, formulations with iodine such as povidone-iodine (PVP-I) were shown as effective in inactivating SARS-CoV-2 virus. This study describes a new formulation consisting in a carboxymethylstarch:iodine complex (CMS:I2) as an alternative to the synthetic polymer polyvinylpyrrolidone-iodine for virucidal activity. It was previously reported that CMS:I2 demonstrated high mucoadhesive properties and a remarkable sprayability, favoring the oropharyngeally administration. Herein, CMS:I2 was shown to exert a strong antiviral activity against human coronavirus hCoV-OC43 - an accepted model mimicking the SARS-CoV-2 virus. The virucidal activity of CMS:I2 and of other iodine compounds was quantitatively assessed against the luciferase-expressing hCoV-OC43RLuc virus, using the luciferase-based infectivity assay and cell target HRT-18. This virucidal activity of CMS:I2 was found to be importantly increased upon the addition of salivary α-amylase by on-site hydrolysis of the CMS:I2 and release of iodine, supporting the assumption that the alpha-amylase is the main factor from saliva triggering its virucidal action. Importantly, none of the tested CMS:I2 formulations presented an impact on cell viability assessed by XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide) assay. It is suggested that CMS:I2 formulations could prevent the initial phases of various respiratory viruses, including SARS-CoV-2 infection by possibly interfering with viral attachment and entry into target cells.