The effects of ethyl lauroyl arginine hydrochloride( ELAH) in nasal spray on SARS-C0V-2

In 2019, a coronavirus caused an outbreak of severe respiratory syndrome in Wuhan, China, and the virus was identified as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The aim of the study was to investigate the broad-spectrum antiviral effects of ethyl lauroyl arginine hydrochloride (ELAH) against SARS-CoV-2 in vitro and in cell cultures. In vitro treatment of pseudovirus VSV-SARS-CoV-2 expressing the receptor binding domain of SARS-CoV-2 for 10 minutes at 37°C with 15 µg/ml and 110 µg/ml ELAH inhibited virus replication in Vero cells by 55% and over 90%, respectively. Intranasal administration of Syrian golden hamsters with SARS-CoV-2 pretreated in vitro with ELAH for 10 minutes at 37°C not only inhibited the disease symptoms typically caused by SARS-CoV-2 in hamsters but also concomitantly reduced the total RNA viral load and the subgenomic RNA compared with the control non-ELAH group. In vitro treatment of the Delta variant of SARS-CoV-2 at 37°C for 10 minutes with 200 µg/ml ELAH inhibited replication in Vero E6 TMPRS-2 cells by 2 logs. To elucidate the mechanism of the action of ELAH, MRC-5 cells were pretreated with various concentrations of ELAH followed by infection with HCoV-229E. The data presented show that ELAH inhibited the cytopathic effects induced by the virus in MRC-5 cells. High-resolution electron microscopy of MRC-5 cells pretreated with ELAH prior to infection showed significantly reduced progeny virions on the surface of the infected cells. These results suggest that the primary mode of action of ELAH in MRC-5 cells is most likely due to the lack of attachment of the virus to the aminopeptidase N (APN) receptor, thus affecting the entry and subsequent replication of the virus in infected cells. The results presented in this study suggest that ELAH in nasal spray formula could be a promising virucidal agent for the prevention of coronavirus infections, including SARS-CoV-2 infections through the nasopharynx.