SARS-CoV-2 protein ORF3a is pathogenic in Drosophila and causes phenotypes associated with COVID-19 post-viral syndrome

BioRxiv : the Preprint Server for Biology
Shuo YangAaron N Johnson

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic has caused millions of deaths and will continue to exact incalculable tolls worldwide. While great strides have been made toward understanding and combating the mechanisms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, relatively little is known about the individual SARS-CoV-2 proteins that contribute to pathogenicity during infection and that cause neurological sequela after viral clearance. We used Drosophila to develop an in vivo model that characterizes mechanisms of SARS-CoV-2 pathogenicity, and found ORF3a adversely affects longevity and motor function by inducing apoptosis and inflammation in the nervous system. Chloroquine alleviated ORF3a induced phenotypes in the CNS, arguing our Drosophila model is amenable to high throughput drug screening. Our work provides novel insights into the pathogenic nature of SARS-CoV-2 in the nervous system that can be used to develop new treatment strategies for post-viral syndrome. SARS-CoV-2 ORF3a is pathogenic in the nervous system.ORF3a induces cell death, inflammation, and lysosome dysfunction.Chloroquine protects against ORF3a induced CNS distress and lysosome dysfunction.

Citations

Apr 3, 2021·International Journal of Molecular Sciences·J Michael HarnishShinya Yamamoto

Methods Mentioned

BETA
transgenic

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