The role of the SARS‐CoV‐2 envelope protein as a pH‐dependent cation channel

Trobec, Tomaž

doi:10.1113/jp281785

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…Our simulations with the external electric field suggest that the pore is anion selective, contrary to what has been reported to date in literature ( Trobec, 2021 ). Experimentally, in order to characterize the E-2 protein, we reconstructed the lipid system at pH 6, in order to mimic the ERGIC environment, which has a slightly acidic pH, normally between 6 and 7 ( Medeiros-Silva et al, 2022 ).…”

Section: Discussioncontrasting

confidence: 99%

Electrophysiological properties and structural prediction of the SARS-CoV-2 viroprotein E

Cubisino,

Milenkovic,

Conti-Nibali

et al. 2024

Front. Mol. Biosci.

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COVID-19, the infectious disease caused by the most recently discovered coronavirus SARS- CoV-2, has caused millions of sick people and thousands of deaths all over the world. The viral positive-sense single-stranded RNA encodes 31 proteins among which the spike (S) is undoubtedly the best known. Recently, protein E has been reputed as a potential pharmacological target as well. It is essential for the assembly and release of the virions in the cell. Literature describes protein E as a voltage-dependent channel with preference towards monovalent cations whose intracellular expression, though, alters Ca2+ homeostasis and promotes the activation of the proinflammatory cascades. Due to the extremely high sequence identity of SARS-CoV-2 protein E (E-2) with the previously characterized E-1 (i.e., protein E from SARS-CoV) many data obtained for E-1 were simply adapted to the other. Recent solid state NMR structure revealed that the transmembrane domain (TMD) of E-2 self-assembles into a homo-pentamer, albeit the oligomeric status has not been validated with the full-length protein. Prompted by the lack of a common agreement on the proper structural and functional features of E-2, we investigated the specific mechanism/s of pore-gating and the detailed molecular structure of the most cryptic protein of SARS-CoV-2 by means of MD simulations of the E-2 structure and by expressing, refolding and analyzing the electrophysiological activity of the transmembrane moiety of the protein E-2, in its full length. Our results show a clear agreement between experimental and predictive studies and foresee a mechanism of activity based on Ca2+ affinity.

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Section: Discussioncontrasting

confidence: 99%

Electrophysiological properties and structural prediction of the SARS-CoV-2 viroprotein E

Cubisino,

Milenkovic,

Conti-Nibali

et al. 2024

Front. Mol. Biosci.

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“…It has been proposed that viroporins action might lead to an increase of cytosolic pH by de-acidification of the ER-Golgi intermediate compartment (ERGIC). Use of this mechanism was suggested for IAV M2 ( Ciampor et al, 1992 , Ciampor et al, 1992 , Sakaguchi et al, 1996 ), HCV p7 ( Wozniak et al, 2010 , Breitinger et al, 2016 ), infectious Bronchitis CoV (IBV) envelope protein ( Westerbeck and Machamer 2019 ) and SARS CoV-2 E protein ( Nieto-Torres et al, 2015 , Cabrera-Garcia et al, 2021 , Trobec, 2021 ). In all these cases, shunting of pH may help to protect acid-labile proteins or particles during viral release.…”

Section: General Architecture and Function Of Viroporinsmentioning

confidence: 99%

Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2

Farag

Sticht

Breitinger

2022

The International Journal of Biochemistry & Cell Biology

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“…Serving as an important membrane component, the M protein forms a dimer that mediates virus assembly, budding, and release [40]. The E protein serves as a pH-dependent cation channel, and is important for viral pathogenesis and assembly [41]. Together with the M protein, the E protein regulates maturation and retention of the S protein, thereby promoting assembly of SARS-CoV-2 viral particles [42].…”

Section: Structures and Viral Proteins Of Pathogenic Human Covsmentioning

confidence: 99%

Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses

Yang,

Li,

2024

J Nanobiotechnol

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Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens. Graphical abstract

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The role of the SARS‐CoV‐2 envelope protein as a pH‐dependent cation channel

Abstract: support-information-section).

Cited by 4 publications

References 5 publications

Electrophysiological properties and structural prediction of the SARS-CoV-2 viroprotein E

Electrophysiological properties and structural prediction of the SARS-CoV-2 viroprotein E

Viroporins: Structure, function, and their role in the life cycle of SARS-CoV-2

Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses

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