Evidence map›Paper›PMID 33574281›Full record

ArticleNature communications2021

A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry.

Yunkai Zhu, Fei Feng, Gaowei Hu, Yuyan Wang, Yin Yu, Yuanfei Zhu, Wei Xu, Xia Cai, Zhiping Sun, Wendong Han and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 3 pooled it
16.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

198 citing papers in PubMed, 3 syntheses or guidelines pooled it, 291 citations in OpenAlex.

  1. Pooled it
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  9. Viral syncytia evolve to resist interferon.Nature communications · 2026
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138 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

Yunkai Zhu *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Fei Feng *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Gaowei Hu *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Yuyan Wang *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Yin YuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Yuanfei ZhuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Wei XuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Xia CaiKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Zhiping SunKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Wendong HanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Rong YeKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Di QuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Qiang DingCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.ORCID 0000-0002-6226-869X
Xinxin HuangTechnical Center For Animal, Plant and Food Inspection and Quarantine of Shanghai Customs, Shanghai, China.
Hongjun ChenShanghai Veterinary Research Institute, CAAS, Shanghai, China.
Wei XuGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Youhua XieKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.ORCID 0000-0002-2416-7708
Qiliang CaiKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. qiliang@fudan.edu.cn.ORCID 0000-0002-7147-0953
Zhenghong YuanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. zhyuan@shmu.edu.cn.ORCID 0000-0003-0268-4891
Rong ZhangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. rong_zhang@fudan.edu.cn.ORCID 0000-0003-2941-4808
Shanghai Medical College of Fudan University · CNShanghai Customs College · CNShanghai Veterinary Research Institute · CNTsinghua University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.

Indexed as

CRISPR-Cas SystemsGenome-Wide Association StudyHost-Pathogen InteractionsVirus InternalizationA549 CellsAngiotensin-Converting Enzyme 2AnimalsChlorocebus aethiopsCOVID-19Disease Models, AnimalEndosomesHeLa CellsHumansMesocricetusSARS-CoV-2Serine EndopeptidasesACE2 protein, humanAngiotensin-Converting Enzyme 2Serine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID33574281
PMCPMC7878750
OpenAlexW3128335178

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.