Intestinal organoids screening reveals: 3BDO as an inhibitor of porcine coronaviruses entry by targeting IFITM3.

Abstract

Porcine coronaviruses pose a major threat to the global pig industry, causing severe disease and high mortality in piglets. Despite the implementation of various control measures, these viruses continue to hinder the sustainable development of pig farming. To better control the prevalence of porcine coronaviruses, we utilized intestinal organoids as a drug-screening platform to identify effective and safe antiviral agents. The results showed that 3BDO significantly inhibits transmissible gastroenteritis virus (TGEV) infection in intestinal organoid monolayers, with a 50 % inhibitory concentration (IC₅₀) of 14.6 µM and a high selectivity index (SI = 87.67). Further analyses suggested that 3BDO inhibits TGEV internalization, which is associated with its ability to enhance the protein abundance of interferon-induced transmembrane protein 3 (IFITM3), a well-known inhibitor of virus-cell membrane fusion. Consistently, knockdown of IFITM3 abolished the antiviral activity of 3BDO. Moreover, 3BDO also inhibited porcine epidemic diarrhea virus (PEDV) and porcine respiratory coronavirus (PRCV) entry through the same mechanism. Overall, this study identifies 3BDO as a promising antiviral candidate for the prevention and control of porcine coronaviruses infections.