Genome-wide characterization of SARS-CoV-2 cytopathic proteins in the search for antiviral targets

Therapeutic inhibition of key viral functions is critical for reducing coronavirus disease 2019 (COVID-19)

We sought to identify antiviral targets through genome-wide identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins that are critical for viral pathogenesis and cause deleterious cytopathic effects

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has claimed more than 5.

While current vaccines are effective in preventing SARS-CoV-2 infection, breakthrough infections are not uncommon

2) It is one of seven human coronaviruses (HCOVs) that cause human illnesses ranging from the common cold to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)

We believe that SARS-CoV-2 protein therapeutic targets (i) are critical for viral survival, (ii) contribute to viral pathogenesis, (iii) produce measurable cytopathic effects and can be used as high-throughput Endpoints for drug screening, and (iv) can be established or novel antiviral drug targets

4) to clone genes representing the entire viral genome into the fission yeast gene expression system (6,13).
The expression of each viral ORF is controlled by the inducernoMetermessage inputtThiamine (nmt1) Promoter (13), so that all SARS-CoV-2-specific viral protein effects can be specifically measured by gene induction rather than by methods without gene induction (6,8) Using this unique integration strategy, we report the identification of multiple potential viral therapeutic targets and describe the concept of ORF3a in detail
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We demonstrate the potential of ORF3a as a therapeutic target for the discovery and testing of antiviral drugs against COVID-19
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