tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2017 Jun 28. pii: S0960-894X(17)30687-X. doi: 10.1016/j.bmcl.2017.06.074. [Epub ahead of print]
[h=1]Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin.[/h] Wright ZVF[SUP]1[/SUP], Wu NC[SUP]2[/SUP], Kadam RU[SUP]2[/SUP], Wilson IA[SUP]3[/SUP], Wolan DW[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza is a highly contagious respiratory viral infection responsible for up to 50,000 deaths per annum in the US alone. The need for new therapeutics with novel modes of action is of paramount importance. We determined the X-ray structure of Arbidol with influenza hemagglutinin and found it was located in a distinct binding pocket. Herein, we report a structure-activity relationship study based on the co-complex combined with bio-layer interferometry to assess the binding of our compounds. Addition of a meta-hydroxy group to the thiophenol moiety of Arbidol to replace a structured water molecule in the binding pocket resulted in a dramatic increase in affinity against both H3 (1150-fold) and H1 (98-fold) hemagglutinin subtypes. Our analogues represent novel leads to yield more potent compounds against hemagglutinin that block viral entry.
Copyright ? 2017 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Arbidol; Bio-layer interferometry; Hemagglutinin; Influenza; Structure-based drug design
PMID: 28689973 DOI: 10.1016/j.bmcl.2017.06.074
[h=1]Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin.[/h] Wright ZVF[SUP]1[/SUP], Wu NC[SUP]2[/SUP], Kadam RU[SUP]2[/SUP], Wilson IA[SUP]3[/SUP], Wolan DW[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza is a highly contagious respiratory viral infection responsible for up to 50,000 deaths per annum in the US alone. The need for new therapeutics with novel modes of action is of paramount importance. We determined the X-ray structure of Arbidol with influenza hemagglutinin and found it was located in a distinct binding pocket. Herein, we report a structure-activity relationship study based on the co-complex combined with bio-layer interferometry to assess the binding of our compounds. Addition of a meta-hydroxy group to the thiophenol moiety of Arbidol to replace a structured water molecule in the binding pocket resulted in a dramatic increase in affinity against both H3 (1150-fold) and H1 (98-fold) hemagglutinin subtypes. Our analogues represent novel leads to yield more potent compounds against hemagglutinin that block viral entry.
Copyright ? 2017 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Arbidol; Bio-layer interferometry; Hemagglutinin; Influenza; Structure-based drug design
PMID: 28689973 DOI: 10.1016/j.bmcl.2017.06.074