Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches

Paul, S.; Nadendla, Swathi; Sobhia, M. Elizabeth

doi:10.1021/acs.jpclett.2c01155

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…Exogenous proteins have disadvantages such as low efficiency in drug delivery and immunogenicity, whereas small-molecule ligands pose limitations such as challenges for manufacturing and increased toxicity. Thus, direct interception of the amino acids of ACE2 could be a simple and effective method [38][39][40]. The length of the ACE2-derived peptide (CSNP1) is 16 amino acids [41].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ACE2–S Protein Interaction by a Short Functional Peptide with a Boomerang Structure

Wei,

Liu,

Zhang

et al. 2024

Molecules

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Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 μM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Inhibition of ACE2–S Protein Interaction by a Short Functional Peptide with a Boomerang Structure

Wei,

Liu,

Zhang

et al. 2024

Molecules

View full text Add to dashboard Cite

show abstract

“…Miniature protein conjugates can be used to produce spray and aerosol agents, which can be added to existing delivery methods. Gouda et al ( 99 ) and Basit et al ( 100 ) designed an ACE2-derived peptide that binds well to SARS-CoV-2 in molecular docking, with a binding energy of 154.5 and 13.2 kcal/mol, respectively. Based on the human ACE2 sequence and the RBD region of the S protein of SARS-CoV-2 or SARS-CoV, Chen et al ( 101 ) created a series of peptides, two of which performed well: AYp28 (KKKKKKKVEGFNCYFPLQS) and AYn1 (KKKKKKDKFNHEAEDLFY).…”

Section: Development Of Computational Biology For Sars-cov-2 Inhibito...mentioning

confidence: 99%

“…Miniature protein conjugates can be used to produce spray and aerosol agents, which can be added to existing delivery methods. Gouda et al (99) 101) created a series of peptides, two of which performed well: AYp28 (KKKKKKKVEGFNCYFPLQS) and AYn1 (KKKKKKDKFNHEAEDLFY). In their computational simulations of peptide-protein interactions, the two peptides demonstrated a strong binding affinity to S protein and ACE2.…”

Section: Molecular Docking and Molecular Dynamics Simulationmentioning

confidence: 99%

Recent advances in the exploration and discovery of SARS-CoV-2 inhibitory peptides from edible animal proteins

Kong,

Wang,

Zhong

et al. 2024

Front. Nutr.

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The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), is spreading worldwide. Although the COVID-19 epidemic has passed its peak of transmission, the harm it has caused deserves our attention. Scientists are striving to develop medications that can effectively treat COVID-19 symptoms without causing any adverse reactions. SARS-CoV-2 inhibitory peptides derived from animal proteins have a wide range of functional activities in addition to safety. Identifying animal protein sources is crucial to obtaining SARS-CoV-2 inhibitory peptides from animal sources. This review aims to reveal the mechanisms of action of these peptides on SARS-CoV-2 and the possibility of animal proteins as a material source of SARS-CoV-2 inhibitory peptides. Also, it introduces the utilization of computer-aided design methods, phage display, and drug delivery strategies in the research on SARS-CoV-2 inhibitor peptides from animal proteins. In order to identify new antiviral peptides and boost their efficiency, we recommend investigating the interaction between SARS-CoV-2 inhibitory peptides from animal protein sources and non-structural proteins (Nsps) using a variety of technologies, including computer-aided drug approaches, phage display techniques, and drug delivery techniques. This article provides useful information for the development of novel anti-COVID-19 drugs.

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Reflections after 2 years of COVID‐19 pandemic

Focosi¹,

Casadevall

Maggi

et al. 2022

Reviews in Medical Virology

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Two years into the COVID-19 pandemic, while the world is facing a new surge from another SARS-CoV-2 variant of concern (VOC) and the end of the pandemic is not in clear sight, there is sufficient experience to prevent further communication failures in the current and in future pandemics, and to curb the erosion of trust in science and expertise. 1,2 We attempt here to draw conclusions on several controversial points.(1) The futility of containment. Throughout history, respiratory pathogens associated with low morbidity and mortality, whereby the pathogen can spread from human to human before symptoms become apparent, have never been contained at the population level. The problem is that the vast majority of asymptomatic or mildly symptomatic patients are healthy enough to move around, and thus far there is no easy mechanism for identifying infected individuals who are infectious. Stringent "lockdowns" -which should be communicated as strategies to buy time and protect heath systems from collapse, not to end the viral epidemic -are incompatible with social life as implemented in westernised societies. Thus far, only societies that accept stringent limits to personal freedoms have been able to reduce spread by lockdowns. Limited lockdowns could be less impactful Abbreviations: LMIC, low-to-middle income countries; VOC, variant of concern.

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Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches

Cited by 6 publications

References 48 publications

Inhibition of ACE2–S Protein Interaction by a Short Functional Peptide with a Boomerang Structure

Inhibition of ACE2–S Protein Interaction by a Short Functional Peptide with a Boomerang Structure

Recent advances in the exploration and discovery of SARS-CoV-2 inhibitory peptides from edible animal proteins

Reflections after 2 years of COVID‐19 pandemic

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