Genome-Wide Analysis of the Indispensable Role of Non-structural Proteins in the Replication of SARS-CoV-2

Jun 1, 2022·
Yunyun Jin
Muzi Ouyang (Mia)
Muzi Ouyang (Mia)
,
Ting Yu
,
Jiaxin Zhuang
,
Wenhao Wang
,
Xue Liu
,
Fangfang Duan
,
Deyin Guo
,
Xiaoxue Peng
,
Ji-An Pan
· 0 min read
DOI
Abstract
Understanding the process of replication and transcription of SARS-CoV-2 is essential for antiviral strategy development. The replicase polyprotein is indispensable for viral replication. However, whether all nsps derived from the replicase polyprotein of SARS-CoV-2 are indispensable is not fully understood. In this study, we utilized the SARS-CoV-2 replicon as the system to investigate the role of each nsp in viral replication. We found that except for nsp16, all the nsp deletions drastically impair the replication of the replicon, and nsp14 could recover the replication deficiency caused by its deletion in the viral replicon. Due to the unsuccessful expressions of nsp1, nsp3, and nsp16, we could not draw a conclusion about their in trans-rescue functions. Our study provided a new angle to understand the role of each nsp in viral replication and transcription, helping the evaluation of nsps as the target for antiviral drug development.
Type
Publication
Frontiers in Microbiology, 13, 907422
Status
Peer-reviewed Open access
publications
Muzi Ouyang (Mia)
Authors
PhD Candidate

I am Muzi Ouyang (欧阳木子) — I go by Mia. I am a PhD candidate in Chemistry at Tsinghua University, advised by Prof. Ying Tan (谭英) at the Institute of Biopharmaceutical and Health Engineering (iBHE) in Shenzhen. I work on targeted protein degradation: designing bioPROTACs that recruit E3 ligases to destroy proteins small molecules struggle to drug — and working out why that degradation sometimes fails.

My dissertation has two halves. The first is a dual-target bioPROTAC that co-degrades ERα and PI3K p85α, re-sensitizing tamoxifen-resistant breast cancer cells to endocrine therapy. The second is a KRAS-targeting degrader, where I found a resistance mutation in the hypervariable region that lets KRAS escape a multimerization-dependent platform, and used all-atom molecular dynamics to trace the conformational mechanism behind the escape.

Alongside the wet lab I work in computational protein design — Rosetta, ProteinMPNN and AlphaFold2 — including an end-to-end reproduction of the CLAIRE de novo binder-design pipeline, published openly with its debugging narrative. My training spans animal science, basic medicine and chemistry, which is why I move between wet-lab mechanism and computational design rather than choosing between them.

I expect to defend in June 2027 and am seeking postdoctoral positions starting in late 2027. If my work overlaps with your group’s, I’d be glad to hear from you — I’ll gladly send my CV. Write to me at mumumia.1009@gmail.com, or oymzmia@163.com if you are corresponding from within China.