Bidirectional interplay between SARS-CoV-2 and autophagy

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ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the recent COVID-19 pandemic, continues representing one of the main health concerns worldwide. Autophagy, in addition to its role in cellular homeostasis and metabolism, plays an important part for the host antiviral immunity. However, viruses including SARS-CoV-2 have evolved diverse mechanisms to not only overcome autophagy’s antiviral pressure but also manipulate its machinery in order to enhance viral replication and propagation. Here, we discuss our current knowledge on the impact that autophagy exerts on SARS-CoV-2 replication, as well as the different counteracting measures that this virus has developed to manipulate autophagy’s complex machinery. Some of the elements regarding this interplay may become future therapeutic targets in the fight against SARS-CoV-2.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Origin and evolution of pathogenic coronaviruses

Jie Cui, Fang Li, Zheng-Li Shi (2018)

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

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Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

Jasper Chan, Kin-Hang Kok, Zheng Zhu … (2020)

ABSTRACT A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

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Author and article information

Contributors

Hao Zhou:

ORCID: https://orcid.org/0000-0002-0092-7987

Role: ConceptualizationRole: Writing – original draftRole: Writing – review and editing

Zhiqiang Hu: Role: ConceptualizationRole: Writing – original draftRole: Writing – review and editing

Sergio Castro-Gonzalez:

ORCID: https://orcid.org/0000-0003-4083-7879

Role: ConceptualizationRole: Writing – original draftRole: Writing – review and editing

Vinayaka R. Prasad: Role: Editor

Journal

Journal ID (nlm-ta): mBio

Journal ID (iso-abbrev): mBio

Journal ID (publisher-id): mBio

Title: mBio

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Electronic): 2150-7511

Publication date (Electronic, collection): Jul-Aug 2023

Publication date (Electronic, pub): 12 July 2023

Publication date PMC-release: 12 July 2023

Volume: 14

Issue: 4

Electronic Location Identifier: e01020-23

Affiliations

[1 ] Department of Microbiology and Immunology, College of Medical Technology, Chengdu University of Traditional Chinese Medicine; , Chengdu, China

[2 ] Shandong New Hope Liuhe Agriculture and Animal Husbandry Technology Co., Ltd; , Dezhou, China

[3 ] Biochemistry and Molecular Biology I, University of Granada; , Granada, Spain

Albert Einstein College of Medicine; , Bronx, New York, USA

Author notes

Address correspondence to Sergio Castro-Gonzalez, sergiocastro@ 123456ugr.es

Hao Zhou and Zhiqiang Hu contributed equally to this work. Author order was determined alphabetically.

The authors declare no conflict of interest.

Author information

Hao Zhou https://orcid.org/0000-0002-0092-7987

Sergio Castro-Gonzalez https://orcid.org/0000-0003-4083-7879

Article

Publisher ID: 01020-23 Publisher ID: mbio.01020-23

DOI: 10.1128/mbio.01020-23

PMC ID: 10470609

PubMed ID: 37436071

SO-VID: bd1218a5-b9df-4a7e-a4c1-250ece6860f8

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This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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supplementary-material: 0, authors: 3, Figures: 3, Tables: 1, Equations: 0, References: 112, Pages: 13, Words: 8640

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cover-date July/August 2023

ScienceOpen disciplines: Life sciences

Keywords: autophagy,covid-19,innate immunity,sars-cov-2,therapeutic targets

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ScienceOpen disciplines: Life sciences

Keywords: autophagy, covid-19, innate immunity, sars-cov-2, therapeutic targets

Bidirectional interplay between SARS-CoV-2 and autophagy

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Novel Coronavirus Disease COVID-19

Most cited references 112

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Origin and evolution of pathogenic coronaviruses

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

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