An angiotensin-converting enzyme-2-derived heptapeptide GK-7 for SARS-CoV-2 spike blockade

Han, Songling; Zhao, Gaomei; Wei, Zhuanzhuan; Chen, Yin; Zhao, Jianqi; He, Yiliang; He, Yingjuan; Gao, Jining; Chen, Shilei; Du, Changhong; Wang, Tao; Sun, Wei; Huang, Yi; Wang, Cheng

doi:10.1016/j.peptides.2021.170638

Cited by 16 publications

(21 citation statements)

References 38 publications

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“…Larue et al reported that synthetic peptides SAP1, SAP2, and SAP6 derived from human ACE2 receptor displayed an IC 50 toward SARS-CoV-2 at concentrations of, 2.39, 3.72, and 1.90 mM, respectively, which are much higher than the concentration of 12.1 μM presented by PepKAA. In another study, Han et al reported that the peptide GK-7, also derived from human ACE2, presented an IC 50 toward SARS-CoV-2 at a concentration of 3.8 μM, which is lower than the concentration presented by PepKAA (12.1 μM). It is important to notice that all studies performed the antiviral assay using a pseudovirus expressing the S protein. − In our case, we employed the entire natural virus isolated from a patient with full fitness to infect cells in the assay, which is closer than what occurs during infection.…”

Section: Discussionmentioning

confidence: 93%

“…In another study, Han et al reported that the peptide GK-7, also derived from human ACE2, presented an IC 50 toward SARS-CoV-2 at a concentration of 3.8 μM, which is lower than the concentration presented by PepKAA (12.1 μM). It is important to notice that all studies performed the antiviral assay using a pseudovirus expressing the S protein. − In our case, we employed the entire natural virus isolated from a patient with full fitness to infect cells in the assay, which is closer than what occurs during infection. This could be an explanation for the elevated concentration required for PepKAA to reach the same concentration presented by other peptides.…”

Section: Discussionmentioning

confidence: 93%

“…It is important to notice that all studies performed the antiviral assay using a pseudovirus expressing the S protein. 29 − 31 In our case, we employed the entire natural virus isolated from a patient with full fitness to infect cells in the assay, which is closer than what occurs during infection. This could be an explanation for the elevated concentration required for PepKAA to reach the same concentration presented by other peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, other synthetic peptides have been tested against SARS-CoV-2. − Curreli et al have analyzed the interaction of RBD from SARS-CoV-2 with human ACE2. From this analysis, the authors designed and synthesized four peptides.…”

Section: Discussionmentioning

confidence: 99%

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Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

et al. 2022

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The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted the ability of all peptides to interact with and induce conformational alterations in the spike protein containing the D614G mutation. PepKAA was the most effective peptide, by having the highest docking score regarding the spike protein and reducing the SARS-CoV-2 plaque number by 50% (EC50) at a concentration of 0.15 mg mL–1. Additionally, all peptides had no toxicity to three lines of human cells as well as to zebrafish larvae and embryos. Thus, these peptides have potential activity against SARS-CoV-2, making them promising to develop new drugs to inhibit cell infection by SARS-CoV-2.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

et al. 2022

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“…In the context of viral infection examples such as the FDA-approved peptide Enfurvirtide [16] and further research (reviewed in [17,18]) illustrate the use of peptides as potential agents to block PPIs. In fact, a number of recent publications has shown promising results on the use of peptides to blocks the entrance of SARS-CoV-2 virus using peptides derived from native element of the interaction humanACE2 and SARS-CoV-2 spike [19][20][21] including designed peptides targeting of the heptad repeat 1 region [22], the RBD domain [23][24][25], with validation in cell-cultures [26,27] and tissues [28]. While these approaches rely on the sequence diversification of existing native elements, ours complements these efforts by providing novel sequences (next).…”

Section: Introductionmentioning

confidence: 99%

A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD—ACE2 Interaction

Fernández-Fuentes

Molina

Oliva

2021

IJMS

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The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.

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Protective effect of isoflurane preconditioning on neurological function in rats with HIE

Fei‐Sun

Huang

Qin

et al. 2022

Ibrain

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Hypoxic ischemic encephalopathy (HIE) is an important cause of neonatal death and disability, which can lead to long-term neurological and motor dysfunction. At present, the treatment mainly focuses on the symptomatic treatment in the acute phase and rehabilitation after injury, but the effect is not satisfactory, and more effective methods are urgently needed. Due to the widespread use of inhalation anesthetics in surgery, it has been found that iso urane (ISO) preconditioning may have a positive effect on neuroprotection. The aim of this study was to investigate the effects of ISO preconditioning on neurological function and behavior in HIE rats. MethodsNeonatal rats were used to create hypoxic-ischemic (HI) model by ligating the right common carotid artery at 7 days and then in a hypoxia chamber. The effects of anesthetic drugs on neurological function after one hour of ISO preconditioning were assessed after modeling by Morris water maze(MWM), Ymaze, and rotarod tests at one month. Thereafter, samples were taken at 1 and 42 days for Nissl staining and Hematoxylin-Eosin (HE) staining to observe neuronal number and histomorphology changes. The relationship of behaviour and morphology tests were measured. ResultsIschemia and hypoxia could induce neuronal injury, neurological dysfunction and severe long-term motor function injury. Histological staining and behavioural evaluations were performed to elucidate the pathological changes and neurobehavioural variation after ISO treatment. We found ISO administration signi cantly reduced the infarct volume of brain tissues and improved the autonomous activities of neonatal rats, ISO preconditioning signi cantly reduced neuronal apoptosis induced by HI, reduced cerebral infarction volume, improved histopathological damage of nerve cells, improved long-term cognitive function, and attenuated HI-induced Nissl total cells to reduce and reduce long-term spatial memory impairment caused by hypoxia-ischemia during the maturation of injured brain. ConclusionISO preconditioning can protect the brain injury and promote the recovery of neurological function in neonatal rats with HIE, which may be through inhibiting the neuronal cell death in the cortex and hippocampus after HI.

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An angiotensin-converting enzyme-2-derived heptapeptide GK-7 for SARS-CoV-2 spike blockade

Cited by 16 publications

References 38 publications

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2

A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD—ACE2 Interaction

Protective effect of isoflurane preconditioning on neurological function in rats with HIE

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