Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit

Kandeel, Mahmoud; Yamamoto, Mizuki; Tani, Hideki; Kobayashi, Ayako; Gohda, Jin; Kawaguchi, Yasushi; Kim, Dongbum; Kwon, Hyung‐Joo; Inoue, Jun‐ichiro; Alkattan, Abdullah

doi:10.4062/biomolther.2020.201

Cited by 35 publications

(28 citation statements)

References 44 publications

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“…Coronavirus disease 2019 (COVID-19) is an infectious pandemic disease that has resulted in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 1 ]. The global human death counts due to COVID-19 exceeded 3.9 million to June 2021 [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Adverse drug reactions from two COVID-19 vaccines reported in Saudi Arabia

Alfaleh

Alkattan

Radwan

et al. 2022

Drugs Ther Perspect

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Background Several reports have been published about the impact of coronavirus disease 2019 (COVID-19) vaccines on human health, and each vaccine has a different safety and efficacy profile. The aim of this study was to reveal the nature and classification of reported adverse drug reactions (ADRs) of the two COVID-19 vaccines (tozinameran and ChAdOx1) among citizens and residents living in Saudi Arabia, and show possible differences between the two vaccines and the differences between each batch on the health of populations. Methods A cross-sectional study was conducted in Saudi Arabia between December 2020 and March 2021. Saudi citizens and residents aged ≥ 16 years who had at least one dose of any batch of either of the two approved COVID-19 vaccines (tozinameran and ChAdOx1) and who reported at least one ADR from the vaccines were included. The study excluded people who reported ADRs after receiving tozinameran or ChAdOx1 vaccines but no information was provided about the vaccine’s batch number. Results During the study period, 12,868 vaccinated people, including a high-risk group (i.e., those with chronic illness or pregnant women), reported COVID-19 vaccine ADRs that had been documented in the General Directorate of Medical Consultations, Saudi Ministry of Health. The study reported several ADRs associated with COVID-19 vaccines, with the most common (> 25%) being fever/chills, general pain/weakness, headache, and injection site reactions. Among healthy and high-risk people, the median onset of all reported ADRs for tozinameran and ChAdOx1 vaccine batches were 1.96 and 1.64 days, respectively ( p < 0.01). Furthermore, significant differences ( p < 0.05) were recorded between the two studied vaccines in regard to fever/chills, gastrointestinal symptoms, headache, general pain/weakness, and neurological symptoms, with higher incidence rates of these ADRs observed with the ChAdOx1 vaccine than the tozinameran vaccine. However, the tozinameran vaccine was found to cause significantly ( p < 0.05) more palpitation, blood pressure variations, upper respiratory tract symptoms, lymph node swelling, and other unspecified ADRs than the ChAdOx1 vaccine. Among patients vaccinated with seven different batches of the tozinameran vaccine, people vaccinated with the T4 and T5 batches reported the most ADRs. Conclusion There were significant differences regarding most of the reported ADRs and their onset among tozinameran and ChAdOx1 vaccines on both healthy people and high-risk individuals living in Saudi Arabia. Moreover, the study found that the frequencies of most listed ADRs were statistically different when seven batches of tozinameran vaccine were compared.

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Section: Introductionmentioning

confidence: 99%

Adverse drug reactions from two COVID-19 vaccines reported in Saudi Arabia

Alfaleh

Alkattan

Radwan

et al. 2022

Drugs Ther Perspect

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“…Recently, we designed the first generation of small chemical MERS-CoV fusion inhibitor molecules ( Kandeel et al, 2020 ). In addition, several designed peptides were proven efficient in inhibiting SARS-CoV-2 replication ( Kandeel et al, 2021 ). Complementing these efforts were short peptides demonstrating stronger inhibition in the nanomolar range than the previously provided small molecules, which showed inhibition of MERS-CoV fusion in the low micromolar range.…”

Section: Discussionmentioning

confidence: 99%

Discovery of New Potent anti-MERS CoV Fusion Inhibitors

et al. 2021

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Middle East respiratory syndrome coronavirus (MERS-CoV), capable of zoonotic transmission, has been associated with emerging viral pneumonia in humans. In this study, a set of highly potent peptides were designed to prevent MERS-CoV fusion through competition with heptad repeat domain 2 (HR2) at its HR1 binding site. We designed eleven peptides with stronger estimated HR1 binding affinities than the wild-type peptide to prevent viral fusion with the cell membrane. Eight peptides showed strong inhibition of spike-mediated MERS-CoV cell-cell fusion with IC50 values in the nanomolar range (0.25–2.3 µM). Peptides #4–6 inhibited 95–98.3% of MERS-CoV plaque formation. Notably, peptide four showed strong inhibition of MERS-CoV plaques formation with EC50 = 0.302 µM. All peptides demonstrated safe profiles without cytotoxicity up to a concentration of 10 μM, and this cellular safety, combined with their anti-MERS-CoV antiviral activity, indicate all peptides can be regarded as potential promising antiviral agents.

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“…ppVSV G-SARS-CoV-2 S and human bronchial epithelial, small airway epithelial, and lung cancer cells were utilized to assess infectivity alterations caused by MEK inhibitors (Zhou et al, 2020). Furthermore, PVs were used to test the creation of fusion inhibitor peptides against SARS-CoV-2, and micromolar concentrations of peptides suppressed ppVSV G-SARS-CoV-2 S infection by inhibiting viral fusion (Kandeel et al, 2021). Demethylzeylasteral, another inhibiting drug, can interact with hACE2 and the RBD of the SARS-CoV-2 S protein, thus when tested in ppVSV G-SARS-CoV-2 S, it inhibited ppVSV G-SARS-CoV-2 S entrance into 293T cells (Zhu et al, 2020).…”

Section: Coronavirus Disease Therapeuticsmentioning

confidence: 99%

Pseudotyped Vesicular Stomatitis Virus-Severe Acute Respiratory Syndrome-Coronavirus-2 Spike for the Study of Variants, Vaccines, and Therapeutics Against Coronavirus Disease 2019

et al. 2022

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World Health Organization (WHO) has prioritized the infectious emerging diseases such as Coronavirus Disease (COVID-19) in terms of research and development of effective tests, vaccines, antivirals, and other treatments. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological causative agent of COVID-19, is a virus belonging to risk group 3 that requires Biosafety Level (BSL)-3 laboratories and the corresponding facilities for handling. An alternative to these BSL-3/-4 laboratories is to use a pseudotyped virus that can be handled in a BSL-2 laboratory for study purposes. Recombinant Vesicular Stomatitis Virus (VSV) can be generated with complementary DNA from complete negative-stranded genomic RNA, with deleted G glycoprotein and, instead, incorporation of other fusion protein, like SARS-CoV-2 Spike (S protein). Accordingly, it is called pseudotyped VSV-SARS-CoV-2 S. In this review, we have described the generation of pseudotyped VSV with a focus on the optimization and application of pseudotyped VSV-SARS-CoV-2 S. The application of this pseudovirus has been addressed by its use in neutralizing antibody assays in order to evaluate a new vaccine, emergent SARS-CoV-2 variants (delta and omicron), and approved vaccine efficacy against variants of concern as well as in viral fusion-focused treatment analysis that can be performed under BSL-2 conditions.

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Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit

Cited by 35 publications

References 44 publications

Adverse drug reactions from two COVID-19 vaccines reported in Saudi Arabia

Adverse drug reactions from two COVID-19 vaccines reported in Saudi Arabia

Discovery of New Potent anti-MERS CoV Fusion Inhibitors

Pseudotyped Vesicular Stomatitis Virus-Severe Acute Respiratory Syndrome-Coronavirus-2 Spike for the Study of Variants, Vaccines, and Therapeutics Against Coronavirus Disease 2019

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