JMN3-003

JMN3-003 is a broad-spectrum antiviral inhibitor that acts on host cells rather than directly targeting viral proteins; it exhibits nanomolar-level inhibitory activity against a variety of orthomyxoviruses (Orthomyxoviridae, such as influenza viruses) and paramyxoviruses (Paramyxoviridae, such as respiratory syncytial virus (RSV), mumps virus (MuV) and human parainfluenza virus type 3 (HPIV3)). JMN3-003 blocks viral replication by targeting host factors, thereby helping to reduce the risk of viral resistance developing.

Method: Influenza A/WSN-permissive HT1080, HeLa, MDCK, NIH-3T3, MEL B16 and BHK-21 cells were infected and exposed to serial concentrations of JMN3-003; antiviral EC₅₀ and acute cytotoxicity CC₅₀ values were determined.
Result: JMN3-003 inhibited influenza A/WSN in HT1080 cells with an EC₅₀ of 0.06 ± 0.002 μM. Activity was also detected in HeLa, MDCK and BHK-21 cells, whereas the EC₅₀ was >10 μM in NIH-3T3 and MEL B16 cells; CC₅₀ values were >75 μM in the tested cell lines.^[1].
Method: JMN3-003, designated compound 6p, was evaluated in cell-based antiviral assays against a panel of influenza virus and paramyxovirus family members during medicinal-chemistry lead optimization.
Result: JMN3-003 exhibited broad antiviral activity against the tested myxoviruses, with EC₅₀ values in the low-nanomolar range. ^[2].
Method: A549 cells were treated with 2.5 μM JMN3-003 beginning 1 h before infection with influenza A/WSN/33 at MOI 2. Viral M mRNA was examined after 8 h by single-molecule RNA fluorescence in situ hybridization; 123 control cells and 141 JMN3-003-treated cells were quantified.
Result: JMN3-003 significantly reduced total viral M mRNA levels but did not cause nuclear retention of M mRNA, distinguishing its effect from direct viral mRNA nuclear-export inhibitors.^[3].