LAUSR

Host‐targeting antivirals (HTAs) have received increasing attention for their potential as broad‐spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost‐ and time‐ efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus‐1 (HSV‐1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B‐RAF V600E, reduced viral loads of HSV‐1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV‐1.