Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection

Area of Science:

• Virology
• Cell Biology
• Drug Discovery

Background:

• Zika virus (ZIKV), a re-emerging flavivirus, poses a significant public health threat, notably linked to microcephaly in infants following maternal infection.
• The lack of vaccines and antivirals necessitates a deeper understanding of ZIKV's replication mechanisms to identify therapeutic targets.

Purpose of the Study:

• To investigate the role of the endosomal-lysosomal compartment in the ZIKV life cycle.
• To evaluate the antiviral potential of targeting this compartment.

Main Methods:

• Infection of A549 and SH-SY5Y cells with African and French Polynesia ZIKV strains.
• Treatment with bafilomycin A1 (V-ATPase inhibitor) and U18666A (cholesterol metabolism inhibitor).
• Assessment of viral entry, spread, and maturation.

Main Results:

• Bafilomycin A1 inhibited ZIKV entry and viral spread by affecting maturation.
• U18666A impaired the ZIKV life cycle by targeting late endosomes and lysosomes.
• Both compounds demonstrated antiviral effects through distinct mechanisms targeting the same cellular compartments.

Conclusions:

• The endosomal-lysosomal compartment is crucial for the ZIKV life cycle.
• Targeting this compartment presents a promising strategy for developing novel ZIKV antivirals.