Evidence map›Paper›PMID 30258004›Full record

ArticleJournal of virology2018

Lysosomal Proteases Are a Determinant of Coronavirus Tropism.

Yuan Zheng, Jian Shang, Yang Yang, Chang Liu, Yushun Wan, Qibin Geng, Michelle Wang, Ralph Baric, Fang Li

Registry-linked trialAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04353037 (PATCH 2 & 3), which is not on this map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
10.1field-weighted citation impact, top 2% 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.

NCT04353037 phase2terminatednot on this mapstarted 2020, after this paper: background citation

PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) A Double-blind Placebo Controlled Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19

TypeinterventionalSponsorUnitedHealth GroupRan2020 to 2020Enrolled39ConditionsCoronavirus, Corona Virus InfectionArmsGroup 1 HCQ, Group 2 Placebo
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  7. Journal of virology · 2025
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  13. Review
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  15. Article
  16. The coronavirus recombination pathway.Cell host & microbe · 2023
    Review
  17. Article
  18. Article
  19. Article
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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

9 authors at 2 institutions in 1 country.

Yuan Zheng *Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Jian Shang *Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Yang Yang *Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Chang LiuDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Yushun WanDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Qibin GengDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Michelle WangDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Ralph BaricDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Fang LiDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA lifang@umn.edu.
University of Minnesota · USUniversity of North Carolina at Chapel Hill · US

Funding

Mechanisms of MERS-CoV Entry, Cross-species Transmission and PathogenesisR01AI110700 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, LI, FANG · 2015 to 2024
$7.4M
Receptor recognition mechanisms of coronavirusesR01AI089728 · NIAID · UNIVERSITY OF MINNESOTA · PI Fang Li, Timothy Patrick Sheahan · 2010 to 2026
$4.7M
NIAID NIH HHS R01 AI089728NIAID NIH HHS R01 AI110700
6 · The paper itself

Abstract

Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.

Indexed as

A549 CellsAnimalsCells, CulturedChiropteraChlorocebus aethiopsCoronavirus InfectionsHEK293 CellsHeLa CellsHumansLysosomesMiddle East Respiratory Syndrome CoronavirusPeptide HydrolasesSevere acute respiratory syndrome-related coronavirusSpike Glycoprotein, CoronavirusVero CellsViral TropismPeptide HydrolasesSpike Glycoprotein, Coronaviruscoronavirus spike proteinlysosomal proteasesspecies tropismtissue tropism

Identifiers

PMID30258004
PMCPMC6258935
OpenAlexW2893432007

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.