Synthesis and antiviral property of polysulfate-grafted maleimide-based enediynes

Human coronaviruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose a serious threat to human life and the global economy. To combat emerging viruses and virus variants, it is essential to develop antivirals with non-specific activities. In this study, we report on the synthesis and antiviral properties of four types of polysulfate-grafted maleimide-based enediyne (EDY) molecules. The sulfates in these EDY molecules are designed to target viruses through non-specific electrostatic interactions, providing extracellular viral targeting ability. Meanwhile, the core EDY generates radical species that disintegrate the viral structure proteins, thereby diminishing the infectivity of coronaviruses. Electron paramagnetic resonance spectroscopy confirmed the radical-generating property of enediynes, while antiviral experiments demonstrated that these enediynes exhibit antiviral activity down to micromolar concentrations, suggesting a promising future for this strategy in developing antiviral drugs.