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Molecular Mechanism Underlying the Action of Influenza A Virus Fusion Inhibitor MBX2546

Molecular Mechanism Underlying the Action of Influenza A Virus Fusion Inhibitor MBX2546

Arnab Basu, Gloria Komazin-Meredith, Courtney McCarthy, Aleksandar Antanasijevic, Steven C Cardinale, Rama K Mishra, Dale L Barnard, Michael Caffrey, Lijun Rong, Terry L Bowlin

ACS Infect Dis. 2017 May 12;3(5):330-335.

PMID: 28301927

Abstract:

Influenza A virus envelop protein hemagglutinin (HA) plays important roles in viral entry. We previously have reported that MBX2546, a novel influenza A virus inhibitor, binds to HA and inhibits HA-mediated membrane fusion. In this report, we show that (i) both binding and stabilization of HA by MBX2546 are required for the inhibition of viral infection and (ii) the binding of HA by MBX2546 represses the low-pH-induced conformational change in the HA, which is a prerequisite for membrane fusion. Mutations in MBX2546-resistant influenza A/PR/8/34 (H1N1) viruses are mapped in the HA stem region near the amino terminus of HA2. Finally, we have modeled the binding site of MBX2546 using molecular dynamics and find that the resulting structure is in good agreement with our results. Together, these studies underscore the importance of the HA stem loop region as a potential target for therapeutic intervention.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP695160124	MBX2546		695160-12-4	Price

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