Nipah and Hendra Viruses Use an Adjustable Latch in Receptor Engagement

Area of Science:

• Virology
• Structural Biology
• Drug Discovery

Background:

• Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses.
• Henipaviruses, a type of paramyxovirus, rely on surface glycoproteins for cell entry.
• Targeting these glycoproteins is a key strategy for developing antiviral therapies.

Purpose of the Study:

• To investigate the structural dynamics of HeV and NiV attachment glycoproteins.
• To identify key regions involved in viral attachment and cell invasion.
• To provide insights for the development of novel antihenipaviral drugs.

Main Methods:

• Multidisciplinary approach combining structural biology techniques.
• Investigation of attachment glycoprotein structures for HeV and NiV.
• Site-directed mutagenesis of HeV attachment glycoproteins.

Main Results:

• A flexible region, termed loop 240, was identified near the binding site of henipaviral attachment glycoproteins.
• Loop 240 transitions between an open conformation (unliganded) and a closed 'latch' conformation (bound to Ephrin B2).
• Mutagenesis studies revealed the critical role of R242 engagement with Ephrin B2 in the binding mechanism.

Conclusions:

• The dynamic conformational changes of loop 240 are crucial for henipavirus-Ephrin B2 interactions.
• Understanding these dynamics offers new avenues for designing drugs that inhibit henipavirus entry.
• This research advances the development of effective treatments against Nipah and Hendra viruses.