ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor

Souza, Pedro Filho Noronha; Amaral, Jackson L.; Bezerra, Leandro P.; Lopes, Francisco E.S.; Freire, V. N.; Oliveira, José T.A.; Freitas, Cléverson D.T.

doi:10.1080/07391102.2020.1871415

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Souzaet al designed synthetic peptides targeting the RBD of S protein from SARS-CoV-2, and revealed that out of 650 sequences, four sequences strongly bind to RBD, changing its conformation and leading to misplaced contact with ACE2. This result suggested peptides could block the viral attachment in cells [ 14 ]. However, it has been reported that nAbs, targeting RBD and NTD of SARS-CoV-2 S protein in the S1 subunit, which its inhibitory effect is not constant.…”

Section: Discussionmentioning

confidence: 99%

“…For most coronaviruses, the N-terminal domain (NTD) of the S1 subunit attaches to cellular carbohydrates and the C-terminal domain binds to a cellular protein receptor [ 9 , 10 , 11 , 12 , 13 ]. The receptor-binding domain (RBD) in the S1 subunit of SARS-CoV-2 is responsible for viral receptor engagement through with host cell receptor(s), but related studies of coronavirus infection have reported that synthetic peptides targeting the RBD domain from SARS-CoV-2 could block viral entry into cells [ 14 ]. Therefore, RBD is an essential target for the development of viral attachment inhibitors, even including neutralizing antibodies (nAbs).…”

Section: Introductionmentioning

confidence: 99%

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Virtual Screening-Based Peptides Targeting Spike Protein to Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Infection

Wang

Jiao

et al. 2023

Viruses

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Due to the rapid mutation of porcine epidemic diarrhea virus (PEDV), existing vaccines cannot provide sufficient immune protection for pigs. Therefore, it is urgent to design the affinity peptides for the prevention and control of this disease. In this study, we made use of a molecular docking technology for virtual screening of affinity peptides that specifically recognized the PEDV S1 C-terminal domain (CTD) protein for the first time. Experimentally, the affinity, cross-reactivity and sensitivity of the peptides were identified by an enzyme-linked immunosorbent assay (ELISA) and a surface plasmon resonance (SPR) test, separately. Subsequently, Cell Counting Kit-8 (CCK-8), quantitative real-time PCR (qRT-PCR), Western blot and indirect immunofluorescence were used to further study the antiviral effect of different concentrations of peptide 110766 in PEDV. Our results showed that the P/N value of peptide 110766 at 450 nm reached 167, with a KD value of 216 nM. The cytotoxic test indicated that peptide 110766 was not toxic to vero cells. Results of the absolute quantitative PCR revealed that different concentrations (3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, 200 μM) of peptide 110766 could significantly reduce the viral load of PEDV compared with the virus group (p < 0.0001). Similarly, results of Western blot and indirect immunofluorescence also suggested that the antiviral effect of peptide 110766 at 3.125 is still significant. Based on the above research, high-affinity peptide 110766 binding to the PEDV S1-CTD protein was attained by a molecular docking technology. Therefore, designing, screening, and identifying affinity peptides can provide a new method for the development of antiviral drugs for PEDV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Virtual Screening-Based Peptides Targeting Spike Protein to Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Infection

Wang

Jiao

et al. 2023

Viruses

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“…Many other viruses present S-like proteins critical to receptor recognition, cell attachment, membrane fusion, and virus entry. HIV and Ebola possess S-like proteins with other names [64] , [69] , [81] , [87] , [88] , [89] , [90] , [91] , [92] , [93] , [94] , [95] . In SARS-CoV-2, the S protein in its trimeric form is found exposed outside the viral particle with an extension of 15 nm playing an essential role in viral infection.…”

Section: The S Proteinmentioning

confidence: 99%

The spike glycoprotein of SARS-CoV-2: A review of how mutations of spike glycoproteins have driven the emergence of variants with high transmissibility and immune escape

Souza

Mesquita

Amaral

et al. 2022

International Journal of Biological Macromolecules

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“…Therefore, novel approaches are needed to find synthetic molecules that bind to the ACE2 on the virus spike protein binding surface and are capable of blocking the spike protein-ACE2 interaction yet having no effect on ACE2 enzymatic activity. Recent computational studies have reported certain peptides binding to this interphase that can block the virus spike protein-ACE2 interaction [22][23][24]. While certain peptides [14][15][16][17] and antibodies [18,19] reported seeming to bind to this interphase area, none of them has been developed into actual drugs thus far, indicating that avoiding ACE2-related side effects is a daunting task.…”

Section: Introductionmentioning

confidence: 99%

“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

Shukla

Rustagi

Gao

et al. 2021

IJMS

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Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans

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ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor

Cited by 9 publications

References 39 publications

Virtual Screening-Based Peptides Targeting Spike Protein to Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Infection

Virtual Screening-Based Peptides Targeting Spike Protein to Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Infection

The spike glycoprotein of SARS-CoV-2: A review of how mutations of spike glycoproteins have driven the emergence of variants with high transmissibility and immune escape

“Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

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