Key result
Liposome-encapsulated maduramycin and endusamycin fully protect mice against JEV by targeting actin filaments.
Why the study?
RNA viruses have high mutation rates, and the viral target approach to drug development is inadequate for addressing an increasing diversity of viruses.
Do maduramycin and endusamycin inhibit viral replication and protect against viral infection in preclinical models?
Do maduramycin and endusamycin inhibit viral replication and protect against viral infection in preclinical models?
Maduramycin and endusamycin demonstrate broad-spectrum antiviral activity against multiple RNA viruses by targeting actin filaments, offering potential new antiviral therapies.
Hypothesis-generating for actin-targeting antivirals; should not yet inform clinical practice.
RNA viruses have high mutation rates and constitute an increasing global risk. As the viral target approach to develop antiviral drugs is inadequate for responding to an increasing diversity of viruses, an urgent need exists for the development of new antivirals to prevent future outbreaks. Here, we show that aglycone ionophores maduramycin (Mad) and endusamycin (End) from Streptomyces are broadly virucidal against cytoplasmic replicated viruses, including Japanese encephalitis virus (JEV), rabies virus, hepatitis C virus, vesicular stomatitis virus, hantavirus, dengue virus, Zika virus, chikungunya virus, and SARS-CoV-2 in vitro. Mechanistic studies suggest Mad and End can target actin filaments and displace the DNase-I-binding loop (D-loop) into an outward conformation for stabilizing actin filaments and primarily inhibit viral replication. Liposome-encapsulated Mad or End fully protects mice against JEV infection in vivo. Thus, our results may provide potential and naturally produced antivirals to prevent the spread of viruses in animals.
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Huang et al. (2025) studied Viral infections (JEV, rabies, HCV, VSV, hantavirus, dengue, Zika, chikungunya, SARS-CoV-2). Aglycone ionophores maduramycin (Mad) and endusamycin (End) was evaluated on Viral replication and in vivo protection against JEV infection. Liposome-encapsulated maduramycin and endusamycin fully protected mice against JEV infection in vivo and demonstrated broad-spectrum antiviral activity in vitro by targeting actin filaments.
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