Antiviral effect and mechanism of metformin against grouper iridovirus infection

Singapore grouper iridovirus (SGIV) infection is associated with high mortality in mariculture, and effective treatments are urgently required. Given the wide-ranging applications of metformin, we aimed to assess the effects of metformin against SGIV. The safe and effective concentration of metformin in grouper spleen cells was determined as 250 mu g/mL. We detected the inhibitory activity of metformin against SGIV infection in grouper spleen cells using an aptamer-based fluorescent molecular probe and reverse transcription-quantitative real-time polymerase chain reaction. Metformin effectively inhibited SGIV infection in a dose-dependent manner and showed an excellent inhibitory effect against SGIV in vitro (70%). We further investigated metformin's possible antiviral mechanism and showed that metformin did not damage SGIV invading host cells, but could damage SGIV particles (59.57%) and interfere with SGIV binding (23.25%) and replication (29.48%) in host cells. Metformin mainly inhibited SGIV by damaging SGIV particles. Overall, these results suggested that metformin had direct and host-mediated antiviral effects against SGIV and thus had great potential for the development of effective drugs to control SGIV infection in aquaculture.