Evidence map›Paper›PMID 34663909›Full record

ArticleCell research2021

SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation.

Gang Xu, Ying Li, Shengyuan Zhang, Haoran Peng, Yunyun Wang, Dekang Li, Taijie Jin, Zhuohao He, Yilun Tong, Chunting Qi and 11 more

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

Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

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3 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

21 authors at 6 institutions in 1 country.

Gang Xu *Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Ying Li *Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.ORCID http://orcid.org/0000-0002-3506-1255
Shengyuan Zhang *Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Haoran Peng *Department of Microbiology, Second Military Medical University, 800 Xiangyin Rd, Shanghai, China.
Yunyun Wang *Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Dekang LiInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Taijie JinInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Zhuohao HeInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Yilun TongInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Chunting QiInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Guowei WuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Kangyun DongInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.
Jizhou GouDepartment for Pathology, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China.
Yang LiuInstitute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Tongyang XiaoInstitute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Jing QuInstitute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Nanshan, Shenzhen, Guangdong, China.
Liang LiInstitute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Nanshan, Shenzhen, Guangdong, China. liang.li@siat.ac.cn.ORCID http://orcid.org/0000-0003-1001-7837
Liang LiuDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 907505@qq.com.
Ping ZhaoDepartment of Microbiology, Second Military Medical University, 800 Xiangyin Rd, Shanghai, China. pnzhao@163.com.
Zheng ZhangInstitute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China. zhangzheng1975@aliyun.com.ORCID http://orcid.org/0000-0002-3544-1389
Junying YuanInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China. junying_yuan@sioc.ac.cn.ORCID http://orcid.org/0000-0003-2405-6036
Chinese Academy of Sciences · CNSouthern University of Science and Technology · CNHuazhong University of Science and Technology · CNSecond Military Medical University · CNShenzhen Institutes of Advanced Technology · CNShenzhen Third People’s Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.

Indexed as

Angiotensin-Converting Enzyme 2AnimalsCoronavirus RNA-Dependent RNA PolymeraseCOVID-19COVID-19 Drug TreatmentCytokinesDown-RegulationErbB ReceptorsHumansImidazolesIndolesLungMiceMice, TransgenicMutationReceptor-Interacting Protein Serine-Threonine KinasesACE2 protein, humanAngiotensin-Converting Enzyme 2Coronavirus RNA-Dependent RNA PolymeraseCytokinesEGFR protein, mouseErbB ReceptorsImidazolesIndolesnecrostatin-1NSP12 protein, SARS-CoV-2Receptor-Interacting Protein Serine-Threonine KinasesRipk1 protein, mouse

Identifiers

PMID34663909
PMCPMC8522117
OpenAlexW3205662191

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.