Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin.

Area of Science:

• Virology
• Infectious Diseases
• Pharmacology

Background:

• Emergence of virulent SARS-CoV-2 variants complicates COVID-19 pandemic control.
• Understanding replication dynamics of Alpha (A), Beta (B), and Delta (D) variants is crucial.

Purpose of the Study:

• To assess replication dynamics of SARS-CoV-2 variants A, B, and D in single and co-infections.
• To evaluate the effectiveness of thapsigargin (TG) as a broad-spectrum antiviral against these variants.

Main Methods:

• Infection performance assessment of SARS-CoV-2 variants A, B, and D in vitro.
• Evaluation of viral replication rates and spread in single and co-infection models.
• Testing the efficacy of thapsigargin (TG) in blocking single and co-infections, both prophylactically and therapeutically.

Main Results:

• The Delta (D) variant demonstrated the highest replication rate and cell-to-cell spread.
• Co-infection with the D variant boosted partner variant replication, and synergistic effects were observed in AD and AB co-infections.
• All SARS-CoV-2 variants were highly sensitive to thapsigargin (TG), with >95% inhibition of single and co-infections.

Conclusions:

• The Delta variant's high replication and co-infection synergy pose significant challenges.
• Thapsigargin (TG) is a potent host-centric antiviral effective against a spectrum of contemporary SARS-CoV-2 variants, including in co-infections.
• TG shows promise for managing infections caused by emerging and potentially synergistic SARS-CoV-2 variants.