Richard Zhao
University of Maryland, Baltimore, MD·Microbiology & Immunology
Vaccines against COVID-19 work, but protection wanes over time and new SARS-CoV-2 variants keep appearing. Antiviral drugs are an alternative, yet their success has been uneven and drug resistance is a worry, so new antivirals are still needed for COVID-19 and for lingering post-COVID complications.
- Fields
Microbiology & Immunology
Pharmacology
Biochemistry
- Topics
SARS-CoV-2
ORF3a
antiviral drug discovery
- Grants
- 1 known grant, through Apr 2027
What they work on
- Conduct a genome-wide search for human suppressive cellular proteins that counteract the damaging effects of the SARS-CoV-2 ORF3a protein, using a fission yeast surrogate system combined with human cells.
- Use a fission yeast-based high-throughput screen to identify small molecule inhibitors of ORF3a, building on the preliminary hit etravirine, an FDA-approved antiviral.
- Test whether inhibiting ORF3a blocks its cytopathic effects in lung and kidney epithelial cells, including oxidative stress and NF-κB-driven production of the inflammatory signals TNFα and IL-6 that end in cell death.
- Compare the cytopathic activity of emerging ORF3a mutants to determine how sequence variation relates to cell damage and to inhibitor sensitivity.
More about the research
This project pursues one viral protein, ORF3a, as a drug target. No inhibitors of ORF3a are currently known, which is what makes it an open target.
Why it matters
COVID-19 has infected hundreds of millions of people and caused millions of deaths, and some survivors have lasting lung and kidney problems. Antivirals aimed at ORF3a could offer a treatment option that complements vaccines, and the host proteins and small molecules identified here could become starting points for drugs against COVID-19 and post-COVID syndromes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ke Reid
Wake Forest University, NC·Biochemistry
Test whether the distinct effects of losing Rpl27 paralogs, two gene copies of a large-subunit ribosomal protein, in fission yeast come from differences in protein sequence or in protein abundance.
Yongjie Xu
Wright State University, OH·Genetics
Determine how mutations in the Rad3-Rad26 complex, the RecQ helicase Rqh1, the Smc5/6 complex and RPA impair Rad3 (ATR) checkpoint signaling at stalled replication forks, using fission yeast mutants in vivo and in vitro.
Fei Li
New York University, NY·Genetics
Define how low-level transcription of centromeres into RNA is regulated in fission yeast and what role it plays in centromere function and chromosome segregation.
The school
University of Maryland, Baltimore: 23 labs on PI Pages, $1.5B a year on research, 79 research doctorates a year.
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