Melatonin and other indoles show antiviral activities against swine coronaviruses in vitro at pharmacological concentrations

The current coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights major gaps in our knowledge on the prevention control and cross-species transmission mechanisms of animal coronaviruses. Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine delta coronavirus (PDCoV) are three common swine coronaviruses and have similar clinical features. In the absence of effective treatments, they have led to significant economic losses in the swine industry worldwide. We reported that indoles exerted potent activity against swine coronaviruses, the molecules used included melatonin, indole, tryptamine, and L-tryptophan. Herein, we did further systematic studies with melatonin, a ubiquitous and versatile molecule, and found it inhibited TGEV, PEDV, and PDCoV infection in PK-15, Vero, or LLC-PK1 cells by reducing viral entry and replication, respectively. Collectively, we provide the molecular basis for the development of new treatments based on the ability of indoles to control TGEV, PEDV, and PDCoV infection and spread.