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  1. Article ; Online: Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection.

    Alkafaas, Samar Sami / Abdallah, Abanoub Mosaad / Ghosh, Soumya / Loutfy, Samah A / Elkafas, Sara Samy / Abdel Fattah, Nasra F / Hessien, Mohamed

    Reviews in medical virology

    2022  Volume 33, Issue 1, Page(s) e2403

    Abstract: Emergence of SARS-CoV-2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus-host cell interaction is essential for developing variant- ... ...

    Abstract Emergence of SARS-CoV-2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus-host cell interaction is essential for developing variant-independent therapeutic options. The internalization of SARS-CoV-2, into lung epithelial cells, is mediated by endocytosis, especially clathrin-mediated endocytosis (CME). Although vaccination is the gold standard strategy against viral infection, selective inhibition of endocytic proteins, complexes, and associated adaptor proteins may present a variant-independent therapeutic strategy. Although clathrin and/or dynamins are the most important proteins involved in CME, other endocytic mechanisms are clathrin and/or dynamin independent and rely on other proteins. Moreover, endocytosis implicates some subcellular structures, like plasma membrane, actin and lysosomes. Also, physiological conditions, such as pH and ion concentrations, represent an additional factor that mediates these events. Accordingly, endocytosis related proteins are potential targets for small molecules that inhibit endocytosis-mediated viral entry. This review summarizes the potential of using small molecules, targeting key proteins, participating in clathrin-dependent and -independent endocytosis, as variant-independent antiviral drugs against SARS-CoV-2 infection. The review takes two approaches. The first outlines the potential role of endocytic inhibitors in preventing endocytosis-mediated viral entry and its mechanism of action, whereas in the second computational analysis was implemented to investigate the selectivity of common inhibitors against endocytic proteins in SARS-CoV-2 endocytosis. The analysis revealed that remdesivir, methyl-β-cyclodextrin, rottlerin, and Bis-T can effectively inhibit clathrin, HMG-CoA reductase, actin, and dynamin I GTPase and are more potent in inhibiting SARS-CoV-2 than chloroquine. CME inhibitors for SARS-CoV-2 infection remain understudied.
    MeSH term(s) Humans ; Actins/metabolism ; COVID-19 ; SARS-CoV-2/metabolism ; Endocytosis/physiology ; Virus Internalization ; Clathrin/metabolism
    Chemical Substances Actins ; Clathrin
    Language English
    Publishing date 2022-11-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1086043-5
    ISSN 1099-1654 ; 1052-9276
    ISSN (online) 1099-1654
    ISSN 1052-9276
    DOI 10.1002/rmv.2403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.

    Alkafaas, Samar Sami / Elsalahaty, Mohamed I / Ismail, Doha F / Radwan, Mustafa Ali / Elkafas, Sara Samy / Loutfy, Samah A / Elshazli, Rami M / Baazaoui, Narjes / Ahmed, Ahmed Ezzat / Hafez, Wael / Diab, Mohanad / Sakran, Mohamed / El-Saadony, Mohamed T / El-Tarabily, Khaled A / Kamal, Hani K / Hessien, Mohamed

    Cancer cell international

    2024  Volume 24, Issue 1, Page(s) 89

    Abstract: Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells ... ...

    Abstract Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein-protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis.
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2091573-1
    ISSN 1475-2867
    ISSN 1475-2867
    DOI 10.1186/s12935-024-03221-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A study on the effect of natural products against the transmission of B.1.1.529 Omicron.

    Alkafaas, Samar Sami / Abdallah, Abanoub Mosaad / Hussien, Aya Misbah / Bedair, Heba / Abdo, Mahmoud / Ghosh, Soumya / Elkafas, Sara Samy / Apollon, Wilgince / Saki, Morteza / Loutfy, Samah A / Onyeaka, Helen / Hessien, Mohamed

    Virology journal

    2023  Volume 20, Issue 1, Page(s) 191

    Abstract: Background: The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, ...

    Abstract Background: The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains.
    Main body: This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine.
    Conclusion: The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19.
    MeSH term(s) Humans ; Biological Products/pharmacology ; Angiotensin-Converting Enzyme 2 ; COVID-19 Vaccines ; Molecular Docking Simulation ; COVID-19 ; SARS-CoV-2 ; Chloroquine ; COVID-19 Drug Treatment
    Chemical Substances Biological Products ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; COVID-19 Vaccines ; Chloroquine (886U3H6UFF)
    Language English
    Publishing date 2023-08-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2160640-7
    ISSN 1743-422X ; 1743-422X
    ISSN (online) 1743-422X
    ISSN 1743-422X
    DOI 10.1186/s12985-023-02160-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity.

    Alkafaas, Samar Sami / Abdallah, Abanoub Mosaad / Hassan, Mai H / Hussien, Aya Misbah / Elkafas, Sara Samy / Loutfy, Samah A / Mikhail, Abanoub / Murad, Omnia G / Elsalahaty, Mohamed I / Hessien, Mohamed / Elshazli, Rami M / Alsaeed, Fatimah A / Ahmed, Ahmed Ezzat / Kamal, Hani K / Hafez, Wael / El-Saadony, Mohamed T / El-Tarabily, Khaled A / Ghosh, Soumya

    BMC public health

    2024  Volume 24, Issue 1, Page(s) 395

    Abstract: Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 ... ...

    Abstract Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 receptor of the host cell membrane to enter. Targeting the SARS-CoV-2 entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes the conversion of sphingolipid (sphingomyelin) to ceramide. Ceramide molecules aggregate/assemble on the plasma membrane to form "platforms" that facilitate the viral intake into the cell. Impairing the ASMase activity will eventually disrupt viral entry into the cell. In this review, we identified the metabolism of sphingolipids, sphingolipids' role in cell signal transduction cascades, and viral infection mechanisms. Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = - 12.58 kcal/mol), emetine (S = - 11.65 kcal/mol), pimozide (S = - 11.29 kcal/mol), carvedilol (S = - 11.28 kcal/mol), mebeverine (S = - 11.14 kcal/mol), cepharanthine (S = - 11.06 kcal/mol), hydroxyzin (S = - 10.96 kcal/mol), astemizole (S = - 10.81 kcal/mol), sertindole (S = - 10.55 kcal/mol), and bepridil (S = - 10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = - 10.43 kcal/mol), making them better options for inhibition.
    MeSH term(s) Humans ; COVID-19 ; Molecular Docking Simulation ; SARS-CoV-2 ; Sphingomyelin Phosphodiesterase/metabolism ; Ceramides/metabolism ; Sphingolipids
    Chemical Substances Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; Ceramides ; Sphingolipids
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041338-5
    ISSN 1471-2458 ; 1471-2458
    ISSN (online) 1471-2458
    ISSN 1471-2458
    DOI 10.1186/s12889-024-17747-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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