Niacin, an active form of vitamin B3, exerts antiviral function by recruiting β-arrestin through GPR109A to activate the phosphorylation of ERK and STAT1 axis.

The emergence of viral infectious diseases poses a significant threat to public health, and thus the development of effective and safe antiviral drugs is becoming an urgent priority in the pandemic era. Niacin is an active form of vitamin B3 and has been used for hyperlipidemia treatment for decades, with well-established safety and pharmacological profiles. In this study, niacin was found to be a promising antiviral agent with both nutritional and therapeutic benefits. Further data showed that niacin could bind to its receptor GPR109A and then recruit β-arrestin to promote the ERK-STAT phosphorylation axis, subsequently leading to the activation of interferon signaling. Therefore, these findings provided evidence for repurposing this well-established drug as an antiviral agent and also highlighted the potential of GPR109A as a novel target in antiviral therapy.IMPORTANCEThe frequent emergence of viral infections is a major concern for global health. Finding safe and effective antiviral treatments has become more urgent than ever. Niacin-a form of vitamin B3-has long been used to treat hyperlipidemia, and its safety is well-established in clinical applications. Notably, this research demonstrates niacin may also work as an antiviral agent, offering both nutritional and therapeutic benefits. Further studies show that niacin binds specifically to a receptor in host cells called GPR109A and then triggers a series of signals inside the cell that ultimately strengthen the host's antiviral interferon system. These findings suggest that this widely available drug could be repurposed to fight against viruses, and that the GPR109A receptor might be a promising new target for antiviral drug development.