Amphipathic nucleoside and non-nucleoside derivatives of pentacyclic aromatic hydrocarbon perylene are known as potent non-cytotoxic broad-spectrum antivirals. Here we report 3-methyl-5-(perylen-3-ylethynyl)-uracil-1-acetic acid and its amides, a new series of compounds based on a 5-(perylen-3-ylethynyl)-uracil scaffold. The compounds demonstrate pronounced in vitro activity against arthropod-borne viruses, namely tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV), in plaque reduction assays with EC values up to 1.9 and 1.3 nM, respectively, and Chikungunya virus (CHIKV) in cytopathic effect inhibition test with EC values up to 3.2 μM. The compounds were active against respiratory viruses as well: inhibited severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in cytopathic effect inhibition test and influenza A virus (IAV) in virus titer reduction experiments - EC values up to 51 nM and 2.2 μM, respectively. The activity is determined by the presence of a hydrophobic perylene core, all of the synthesized compounds exhibited comparable O generation rates. Nonetheless, the activity can vary by orders of magnitude depending on the hydrophilic part of the molecule, suggesting a complex mode of action. Time-of-addition experiment and fluorescent imaging technique indicate that the compounds inhibit viral fusion in dose-dependent manner. Localization of the compound in lipid bilayers and visible damage to viral envelope suggest membrane as primary target. Dramatic reduction of antiviral activity with limited access of light or under treatment with antioxidants further cements the idea of photoinduced ROS-mediated viral envelope damage to be the mode of antiviral action.