Inducers of the NF-κB pathways impair hepatitis delta virus replication and strongly decrease progeny infectivity in vitro

•HDV leads to the most severe form of chronic viral hepatitis and treatment options are limited.•We demonstrate, for the first time, that immune-modulators inducing the NF-κB pathways can inhibit HDV in hepatocytes.•Pam3CSK4 (TLR1/2 agonist) and BS1 (LTBR agonist) reduced the intracellular and extracellular HDV RNAs and proteins.•Pam3CSK4 and BS1 also strongly reduced specific infectivity of remaining HDV virion progeny.•Pam3CSK4 and BS1 will thereby probably counteract viral spreading in vivo.