MBX2546 is a non-cytotoxic (CC50 >100 μM; 283T) molecule that inhibits against influenza hemagglutinin- (HA-) mediated viral entry (IC90 = 5.7 μM against HIV/HA(H5) entry in 293T culture vs. IC90 >100 μM, 98.2 μM, and >85 μM against HIV/LASV-GP, HIV/EBOV-GP, HIV/VSV-G, respectively) by targeting group 1 HA-specific conformational epitope in the HA stem loop region. MBX2546 is shown to inhibit influenza A strains A/PR/8/34 (H1N1) and A/Florida/21/2008 (H1N1-H275Ψ) (oseltamivir-resistant strain), A/California/10/2009/H1N1, as well as high pathogenic avian influenza (HPAI) strain A/Hong Kong/H5N1 (IC50 = 0.3, 5.8, 0.55-1.5, and 3.6 μM, respectively), but not A/Texas/12/2007 (H3N2), A/Perth/16/2009 (H3N2), A/Victoria/3/75 (H3N2), A/Panama/2007/99 (H3N2), A/Sydney/05/97 (H3N2), A/California/7/04 (H3N2), A/Wyoming/03/2003 (H3N2), or influenza B strain B/Florida/4/2006 in MDCK cultures.
Non-cytotoxic molecule that blocks hemagglutinin (HA)-mediated influenza A host entry by targeting group 1 HA stem loop region conformational epitope.
