The structural basis of accelerated host cell entry by SARS‐CoV‐2†

Seyran, Murat; Takayama, Kazuo; Uversky, Vladimir N.; Lundström, Kenneth; Palù, Giorgio; Sherchan, Samendra P.; Attrish, Diksha; Rezaei, Nima; Aljabali, Alaa A. A.; Ghosh, Shinjini; Pizzol, Damiano; Chauhan, Gaurav; Adadi, Parise; El-Aziz, Tarek Mohamed Abd; Soares, António; Kandimalla, Ramesh; Tambuwala, Murtaza M.; Hassan, Sk. Sarif; Azad, Gajendra Kumar; Choudhury, Pabitra Pal; Baetas‐da‐Cruz, Wagner; Serrano‐Aroca, Ángel; Brufsky, Adam; Uhal, Bruce D.

doi:10.1111/febs.15651

Cited by 138 publications

(139 citation statements)

References 48 publications

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“…To infect respiratory cells, a SARS-CoV-2 Spike (S) protein engages the angiotensin-converting enzyme 2 (ACE2) and also employs two cellular proteases, furin and transmembrane serine protease 2 (TMPRSS2), for viral entry [ 5 , 6 , 7 ]. Notably, ACE2 expression has been shown to correlate with susceptibility to SARS-CoV-S-driven entry [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients

et al. 2021

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The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNβ stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients

et al. 2021

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“…Murat Seyran et al identified the structural bases underlying the pandemic potential of SARS-CoV-2, and its rapid movement over respiratory epithelia that enables rapid cellular entry is clarified [ 89 ]. They suggested that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit contributes to more successful initial contact and association with the sialic acid layer over the epithelium based on prominent viral spike (S) protein characteristics, so this, in fact, enables faster viral 'surfing' of the epithelium and SARS-CoV-2 receptor scanning [ 89 ]. The primary entry receptor for SARS-CoV-2 is an ACE-2 protein on the epithelial surface, and protein-protein interaction assays showed high-affinity binding of the S protein to ACE-2 [ 89 ].…”

Section: Lopinavir/ritonavirmentioning

confidence: 99%

“…They suggested that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit contributes to more successful initial contact and association with the sialic acid layer over the epithelium based on prominent viral spike (S) protein characteristics, so this, in fact, enables faster viral 'surfing' of the epithelium and SARS-CoV-2 receptor scanning [ 89 ]. The primary entry receptor for SARS-CoV-2 is an ACE-2 protein on the epithelial surface, and protein-protein interaction assays showed high-affinity binding of the S protein to ACE-2 [ 89 ]. No high-frequency mutations have been observed to date in the S protein at the C-terminal domain (CTD) of the S1 subunit, where the receptor-binding domain (RBD) is located.…”

Section: Lopinavir/ritonavirmentioning

confidence: 99%

Effective drugs used to combat SARS-CoV-2 infection and the current status of vaccines

Awadasseid¹,

Wu²,

Tanaka³

et al. 2021

Biomedicine & Pharmacotherapy

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“… COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development 2 . The Structural Basis of Accelerated Host Cell Entry by SARS-CoV-2 3 . Questions concerning the proximal origin of SARS‐CoV‐2 4 .…”

mentioning

confidence: 99%

“…Below I have provided suggestions for several such manuscripts that need to be included and discussed: The Structural Basis of Accelerated Host Cell Entry by SARS-CoV-2 1 . The Importance of Research on the Origin of SARS-CoV-2 2 .…”

mentioning

confidence: 99%

Computational screening for potential drug candidates against the SARS-CoV-2 main protease

et al. 2020

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Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

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The structural basis of accelerated host cell entry by SARS‐CoV‐2†

Cited by 138 publications

References 48 publications

SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients

SARS-CoV-2 Entry Genes Expression in Relation with Interferon Response in Cystic Fibrosis Patients

Effective drugs used to combat SARS-CoV-2 infection and the current status of vaccines

Computational screening for potential drug candidates against the SARS-CoV-2 main protease

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