SARS-like WIV1-CoV poised for human emergence

Area of Science:

• Virology
• Infectious Disease Epidemiology
• Genomics

Background:

• Zoonotic outbreaks threaten public health and economies.
• Metagenomic data exists, but tools to predict viral emergence are lacking.
• Understanding the pandemic potential of novel viruses is crucial.

Purpose of the Study:

• To develop and validate a platform for assessing zoonotic virus emergence and pathogenicity.
• To evaluate the pandemic potential of severe acute respiratory syndrome (SARS)-like viruses, specifically the WIV1-coronavirus (CoV) cluster.
• To identify potential therapeutic interventions against emerging zoonotic threats.

Main Methods:

• Combined existing metagenomic data with reverse genetics to engineer viral reagents.
• Assessed the in vitro and in vivo emergence and pathogenic potential of WIV1-CoVs.
• Evaluated the efficacy of existing SARS monoclonal antibodies and vaccine approaches.

Main Results:

• The WIV1-CoV cluster demonstrated direct human cell infection capability.
• Limited human transmission potential was observed, but in vivo attenuation suggests further adaptation is needed for epidemic spread.
• Monoclonal antibodies were effective in limiting WIV1-CoV infection, while current vaccine approaches were not evaluated as effective.

Conclusions:

• The developed platform is useful for identifying and prioritizing prepandemic strains in animal reservoirs.
• WIV1-CoVs represent a documented threat for potential emergence in human populations.
• Monoclonal antibodies present a viable therapeutic strategy against WIV1-CoV infections.