Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation

Area of Science:

• Virology
• Molecular Biology
• Pathogen Evolution

Background:

• The COVID-19 pandemic is driven by SARS-CoV-2, with evolving variants of concern.
• The B.1.617.2/Delta variant emerged during a major COVID-19 surge in India.
• Virological characteristics of the Delta variant remain largely uncharacterized.

Purpose of the Study:

• To investigate the virological properties of the SARS-CoV-2 B.1.617.2/Delta variant.
• To determine the role of the P681R mutation in the Delta variant's phenotype.
• To assess the pathogenicity of the Delta variant compared to other SARS-CoV-2 strains.

Main Methods:

• Infection of hamsters with the Delta variant and a prototypic SARS-CoV-2 strain.
• Analysis of viral fusogenicity and spike protein cleavage.
• Comparison of pathogenicity between P681R-mutated and parental viruses.

Main Results:

• The B.1.617.2/Delta variant demonstrated significantly higher fusogenicity than prototypic SARS-CoV-2.
• The P681R mutation in the spike protein facilitates spike protein cleavage and enhances viral fusogenicity.
• Delta variant infection led to notably higher pathogenicity in hamsters compared to the parental virus.

Conclusions:

• The P681R mutation is a key determinant of the Delta variant's enhanced pathogenicity.
• Increased viral fusogenicity driven by P681R contributes to the Delta variant's virulence.
• The Delta variant possesses distinct virological properties that may explain its rapid spread and associated disease severity.