An oligomeric approach toward dual-mechanistic, broad-spectrum antiviral effectiveness

We present a comprehensive study of an oligoguanidine family exhibiting remarkable antiviral efficacy against pathogenic viruses. Through structural screening, we identified OG5-11 as a promising compound and thoroughly characterized its antiviral activity using coxsackievirus B3 and spring viremia of carp virus as model viruses. OG5-11 demonstrated a compelling ability to rescue cells already infected with pathogenic viruses at low μM concentrations, as well as a potent and rapid virucidal capacity against infective virions. These effects are likely attributed to the oligomer’s strong affinity towards viral nucleic acids, inhibiting viral replication processes by binding to them. The cationic OG5-11 also exhibited binding capability towards proteins and lipids, directly contributing to its virucidal activity. To evaluate the in vivo efficacy, we assessed OG5-11 in a coxsackievirus B3-based mouse myocarditis model, where it significantly reduced viral burden in the heart tissues by 94%, effectively mitigating viral infection-induced damage. Finally, preliminary investigations demonstrated the potential of the oligoguanidine family to broaden its antiviral spectrum, employing adenovirus and influenza A virus as additional models. Collectively, our findings underscore the effectiveness and inspiration derived from the dual-mechanistic approach of oligomer construction, which holds great promise for the development of urgently needed broad-spectrum antiviral agents.