6UH7

EV-A71 strain 11316 complexed with MADAL compound 30

Summary for 6UH7

• Entry DOI: 10.2210/pdb6uh7/pdb
• EMDB information: 20769
• Descriptor: VP1, VP2, VP3, ... (5 entities in total)
• Functional Keywords: enterovirus, virus, inhibitor
• Biological source: Enterovirus A71; More
• Total number of polymer chains: 4
• Total formula weight: 94901.99

Authors

Lee, H.,Hafenstein, S. (deposition date: 2019-09-26, release date: 2019-12-18, Last modification date: 2024-03-20)

Primary citation

Martinez-Gualda, B.,Sun, L.,Marti-Mari, O.,Noppen, S.,Abdelnabi, R.,Bator, C.M.,Quesada, E.,Delang, L.,Mirabelli, C.,Lee, H.,Schols, D.,Neyts, J.,Hafenstein, S.,Camarasa, M.J.,Gago, F.,San-Felix, A.
Scaffold Simplification Strategy Leads to a Novel Generation of Dual Human Immunodeficiency Virus and Enterovirus-A71 Entry Inhibitors.
J.Med.Chem., 63:349-368, 2020

PubMed Abstract: Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection for which no antiviral therapies are available. We describe here the discovery of potent entry dual inhibitors of HIV and EV71. These compounds contain in their structure three or four tryptophan (Trp) residues linked to a central scaffold. Critical for anti-HIV/EV71 activity is the presence of extra phenyl rings, bearing one or two carboxylates, at the C2 position of the indole ring of each Trp residue. The most potent derivatives, and , inhibit early steps of the replicative cycles of HIV-1 and EV-A71 by interacting with their respective viral surfaces (glycoprotein gp120 of HIV and the fivefold axis of the EV-A71 capsid). The high potency, low toxicity, facile chemical synthesis, and great opportunities for chemical optimization make them useful prototypes for future medicinal chemistry studies.

PubMed: 31809045
DOI: 10.1021/acs.jmedchem.9b01737

Experimental method

ELECTRON MICROSCOPY (2.87 Å)