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  1. Article ; Online: Interactions between ACE2 and SARS-CoV-2 S Protein: Peptide Inhibitors for Potential Drug Developments Against COVID-19.

    Dërmaku-Sopjani, Miribane / Sopjani, Mentor

    Current protein & peptide science

    2021  Volume 22, Issue 10, Page(s) 729–744

    Abstract: Angiotensin-converting enzyme (ACE) shares some homologies with ACE2. However, they are not inhibited by the same inhibitors, but both are associated primarily with the hypertensive disorder through the renin-angiotensin system (RAS). The principal ... ...

    Abstract Angiotensin-converting enzyme (ACE) shares some homologies with ACE2. However, they are not inhibited by the same inhibitors, but both are associated primarily with the hypertensive disorder through the renin-angiotensin system (RAS). The principal activity of ACE2 is to metabolize Ang II into the vasodilatory Ang-(1-7). The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought the ACE2 to the center of attention. This coronavirus uses the host cell ACE2 protein to enter and infect the epithelial cells. In light of the virus's entrance into human cells, the differences in the molecular basis of ACE2 among affected patients may cause their different responses to the virus. Many details about the specific interaction between the viral S protein and ACE2 are already reported. To date, some effective clinically approved vaccines are in use globally, and many others are under development, but no effective specific therapeutic drugs are available against COVID-19. Inhibitors, especially peptide inhibitors, have a great potential to be used for the treatment of COVID-19 and other possible emerging diseases caused by viral pathogens. As a result of the well-known viral protein structures and their host cell targets such as ACE2, antiviral peptides could be appropriately designed and optimized for therapeutic purposes. A better understanding of the structure and pathophysiology of the ACE2 receptor and the interplay between the viral S protein and ACE2 may help to find the solution for the virus treatment. This review summarizes the current understanding of S protein interaction with the ACE2 protein as a potential specific target against SARS-CoV-2 and strategies using peptides against COVID-19.
    MeSH term(s) Angiotensin-Converting Enzyme 2 ; COVID-19 ; Pandemics ; Spike Glycoprotein, Coronavirus
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-08-25
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2045662-1
    ISSN 1875-5550 ; 1389-2037
    ISSN (online) 1875-5550
    ISSN 1389-2037
    DOI 10.2174/1389203722666210916141924
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Molecular Characterization of SARS-CoV-2.

    Dërmaku-Sopjani, Miribane / Sopjani, Mentor

    Current molecular medicine

    2020  Volume 21, Issue 7, Page(s) 589–595

    Abstract: The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats, ... ...

    Abstract The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats, and by yet unknown intermediary animals were transmitted to humans in China 2019. The SARS-CoV-2 spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) but has reduced fatality. At present, the SARS-CoV-2 has caused about 1.16 million deaths with more than 43.4 million confirmed cases worldwide, resulting in a serious threat to public health globally with yet uncertain impact. The disease is transmitted by inhalation or direct contact with an infected person. The incubation period ranges from 1 to 14 days. COVID-19 is accompanied by various symptoms, including cough and fatigue. In most people, the disease is mild, but in some other people, such as in the elderly and people with chronic diseases, it may progress from pneumonia to a multi-organ dysfunction. Many people are reported asymptomatic. The virus genome is sequenced, but new variants are reported. Numerous biochemical aspects of its structure and function are revealed. To date, no clinically approved vaccines and/or specific therapeutic drugs are available to prevent or treat COVID-19. However, there are reported intensive researches on the SARS-CoV-2 to potentially identify vaccines and/or drug targets, which may help to overcome the disease. In this review, we discuss recent advances in understanding the molecular structure of SARS-CoV-2 and its biochemical characteristics.
    MeSH term(s) COVID-19/diagnosis ; COVID-19/etiology ; COVID-19/virology ; Coronavirus/genetics ; Genome, Viral ; Host-Pathogen Interactions/physiology ; Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Internalization ; Virus Replication
    Chemical Substances Viral Proteins
    Language English
    Publishing date 2020-12-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2064873-X
    ISSN 1875-5666 ; 1566-5240
    ISSN (online) 1875-5666
    ISSN 1566-5240
    DOI 10.2174/1566524020999201203213037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Flavonoids derived from medicinal plants as a COVID-19 treatment.

    Sopjani, Mentor / Falco, Francesca / Impellitteri, Federica / Guarrasi, Valeria / Nguyen Thi, Xuan / Dërmaku-Sopjani, Miribane / Faggio, Caterina

    Phytotherapy research : PTR

    2024  Volume 38, Issue 3, Page(s) 1589–1609

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell's receptor protein. ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell's receptor protein. The COVID-19 pandemic had a profound impact on global public health and economies. Although various effective vaccinations and medications are now available to prevent and treat COVID-19, natural compounds derived from medicinal plants, particularly flavonoids, demonstrated therapeutic potential to treat COVID-19 disease. Flavonoids exhibit dual antiviral mechanisms: direct interference with viral invasion and inhibition of replication. Specifically, they target key viral molecules, particularly viral proteases, involved in infection. These compounds showcase significant immunomodulatory and anti-inflammatory properties, effectively inhibiting various inflammatory cytokines. Additionally, emerging evidence supports the potential of flavonoids to mitigate the progression of COVID-19 in individuals with obesity by positively influencing lipid metabolism. This review aims to elucidate the molecular structure of SARS-CoV-2 and the underlying mechanism of action of flavonoids on the virus. This study evaluates the potential anti-SARS-CoV-2 properties exhibited by flavonoid compounds, with a specific interest in their structure and mechanisms of action, as therapeutic applications for the prevention and treatment of COVID-19. Nevertheless, a significant portion of existing knowledge is based on theoretical frameworks and findings derived from in vitro investigations. Further research is required to better assess the effectiveness of flavonoids in combating SARS-CoV-2, with a particular emphasis on in vivo and clinical investigations.
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Plants, Medicinal/metabolism ; Flavonoids/chemistry ; Pandemics ; COVID-19 Drug Treatment ; Antiviral Agents/pharmacology ; Peptidyl-Dipeptidase A/metabolism
    Chemical Substances Flavonoids ; Antiviral Agents ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639136-9
    ISSN 1099-1573 ; 0951-418X
    ISSN (online) 1099-1573
    ISSN 0951-418X
    DOI 10.1002/ptr.8123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Intracellular signaling of the AMP-activated protein kinase.

    Dërmaku-Sopjani, Miribane / Sopjani, Mentor

    Advances in protein chemistry and structural biology

    2019  Volume 116, Page(s) 171–207

    Abstract: AMP-activated protein kinase (AMPK) is an essential cellular energy sensor that senses the cellular energy status and maintains cellular energy balance. The AMPK coordinates cellular and whole-body energy homeostasis through stimulating catabolic ATP- ... ...

    Abstract AMP-activated protein kinase (AMPK) is an essential cellular energy sensor that senses the cellular energy status and maintains cellular energy balance. The AMPK coordinates cellular and whole-body energy homeostasis through stimulating catabolic ATP-producing and suppressing anabolic ATP-consuming intracellular signaling pathways. AMPK induces autophagy and inhibits cell growth in response to starvation, a process that involves regulating certain intracellular signaling molecules. Recent advances demonstrated the AMPK to exert tumor suppressor activity realized through various signaling molecules by stimulating different cellular processes such as apoptosis, autophagy and cell growth and proliferation. AMPK can also be used to protect against metabolic syndrome. AMPK has previously been reported to be either directly or indirectly involved in the regulation of many different cellular transport proteins of high importance for cellular physiology and pathophysiology. Thus, AMPK provides a necessary link between cellular energy metabolism and cellular transport activities. A better understanding of the AMPK role in intracellular signaling under physiological and pathological conditions may represent a potential strategy for developing therapies for treating many different human diseases and disorders, in which AMPK plays a key role.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Apoptosis ; Autophagy ; Cell Proliferation ; Energy Metabolism ; Enzyme Activation ; Humans ; Neoplasms/metabolism ; Signal Transduction
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2019-01-14
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 1876-1631 ; 1876-1623
    ISSN (online) 1876-1631
    ISSN 1876-1623
    DOI 10.1016/bs.apcsb.2018.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The mechanisms underlying the role of Vitex agnus-castus in mastalgia.

    Zeqiri, Aurel / Dermaku-Sopjani, Miribane / Sopjani, Mentor

    Bratislavske lekarske listy

    2022  Volume 123, Issue 12, Page(s) 913–918

    Abstract: Medicinal plants exert therapeutic effects or have beneficial healing functions on the human or animal body. Medicinal plants are widely used in traditional medicine as an interesting alternative and/or complementary to science-based medicine. Compared ... ...

    Abstract Medicinal plants exert therapeutic effects or have beneficial healing functions on the human or animal body. Medicinal plants are widely used in traditional medicine as an interesting alternative and/or complementary to science-based medicine. Compared to chemical drugs, medicinal plants have a lower risk of side effects, are eco-friendly, and have cost-effective production. This encouraged researchers to extensively exploit them for their therapeutic use. One of the most well-known medicinal plants is Vitex agnus-castus L., which belongs to the Verbenaceae family. This shrub tree is mainly grown in tropical and sub-tropical regions. The parts of VAC, especially berries and leaves, contain essential oils, flavonoids, and diterpenes. Many medical benefits of VAC have already been reported, including mastalgia, regulating menstrual cycles and premenstrual complaints, and infertility. Respiratory and cardiovascular effects are also reported. In this review, we will analyze and characterize the known roles of VAC in mastalgia, as well as the mechanism of action reported in in vitro and/or in vivo studies, and show the potential for alternative therapeutic uses in mastalgia, also known as breast pain (Fig. 2, Ref. 40). Keywords: mastalgia, Vitex agnus-castus, therapy, traditional medicine.
    MeSH term(s) Female ; Animals ; Humans ; Vitex/chemistry ; Mastodynia/drug therapy ; Plants, Medicinal ; Plant Extracts/therapeutic use ; Plant Leaves
    Chemical Substances Plant Extracts
    Language English
    Publishing date 2022-09-16
    Publishing country Slovakia
    Document type Review ; Journal Article
    ZDB-ID 127421-1
    ISSN 0006-9248
    ISSN 0006-9248
    DOI 10.4149/BLL_2022_147
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Vasorelaxant Effects of the

    Thaçi, Shpëtim / Krasniqi, Berat / Dërmaku-Sopjani, Miribane / Rifati-Nixha, Arleta / Abazi, Sokol / Sopjani, Mentor

    Evidence-based complementary and alternative medicine : eCAM

    2022  Volume 2022, Page(s) 7708781

    Abstract: This study was undertaken to describe and characterize the relaxing effects of the medicinal ... ...

    Abstract This study was undertaken to describe and characterize the relaxing effects of the medicinal plant
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171158-6
    ISSN 1741-4288 ; 1741-427X
    ISSN (online) 1741-4288
    ISSN 1741-427X
    DOI 10.1155/2022/7708781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Klotho-Dependent Role of 1,25(OH)

    Dërmaku-Sopjani, Miribane / Kurti, Fatbardhë / Xuan, Nguyen Thi / Sopjani, Mentor

    Neuro-Signals

    2021  Volume 29, Issue 1, Page(s) 14–23

    Abstract: The antiaging protein Klotho is encoded by the Klotho gene first identified as an 'aging suppressor', in mice. Klotho deficiency is involved in premature aging and early death, while its overexpression is related to longevity. Klotho is mostly expressed ... ...

    Abstract The antiaging protein Klotho is encoded by the Klotho gene first identified as an 'aging suppressor', in mice. Klotho deficiency is involved in premature aging and early death, while its overexpression is related to longevity. Klotho is mostly expressed in the kidney, but also in the brain, and in other organs. Two forms of Klotho, the cell membrane and secreted form, have pleiotropic activities that include regulation of general metabolism, oxidative stress, and mineral metabolism that correlates with its effect on accelerating aging. Membrane Klotho serves as an obligate co-receptor for the fibroblast growth factor (FGF), while secreted Klotho plays its role as a humoral factor. Klotho protein participates in the regulation of several biological activities, including regulation of calcium-phosphate homeostasis and PTH as well as vitamin D metabolism. The active form of vitamin D, 1,25(OH)
    MeSH term(s) Animals ; Brain/metabolism ; Calcitriol ; Calcium, Dietary ; Glucuronidase/metabolism ; Klotho Proteins ; Mice
    Chemical Substances Calcium, Dietary ; Glucuronidase (EC 3.2.1.31) ; Klotho Proteins (EC 3.2.1.31) ; Calcitriol (FXC9231JVH)
    Language English
    Publishing date 2021-05-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2074039-6
    ISSN 1424-8638 ; 1424-862X
    ISSN (online) 1424-8638
    ISSN 1424-862X
    DOI 10.33594/000000352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Vasorelaxant Effects of the Vitex Agnus-Castus Extract

    Shpëtim Thaçi / Berat Krasniqi / Miribane Dërmaku-Sopjani / Arleta Rifati-Nixha / Sokol Abazi / Mentor Sopjani

    Evidence-Based Complementary and Alternative Medicine, Vol

    2022  Volume 2022

    Abstract: This study was undertaken to describe and characterize the relaxing effects of the medicinal plant Vitex agnus-castus (VAC) extract on isolated rabbit arterial rings. The VAC extracts (VACE) were extracted with ethanol and tested in aorta rings (3-4 mm) ... ...

    Abstract This study was undertaken to describe and characterize the relaxing effects of the medicinal plant Vitex agnus-castus (VAC) extract on isolated rabbit arterial rings. The VAC extracts (VACE) were extracted with ethanol and tested in aorta rings (3-4 mm) of rabbits suspended in an organ bath (Krebs, 37°C, 95% O2/5% CO2) under a resting tension of 1 g to record isometric contractions. After the stabilization period (1-2 hours), contractions were induced by the addition of phenylephrine (0.5 μM) or high KCl (80 mM) and VACE was added on the plateau of the contractions. Experiments were performed to determine the effects and to get insights into the potential mechanism involved in VACE-induced relaxations. The cumulative addition of VACE (0.15–0.75 mg/mL) relaxed, in a concentration-dependent manner, the rabbit aorta rings precontracted either with phenylephrine- or with high KCl thus suggesting calcium channel blocking activities. The VACE effect appeared to be endothelium-dependent. The preincubation with L-NAME (the inhibitor of nitric oxide synthases (NOS)), ODQ (the selective inhibitor of guanylyl cyclase), and indomethacin (the cyclooxygenase inhibitor), downregulated VACE-induced relaxation of aorta rings precontracted with phenylephrine, whereas the bradykinin (stimulator of NOS) and zaprinast (phosphodiesterase inhibitor) further upregulated relaxant effects induced by VACE. These results revealed that the aorta relaxation effect of VACE was mainly endothelium-dependent and mediated by NO/cGMP and prostaglandins synthesis. This vasodilator effect of VACE may be useful to treat cardiovascular disorders, including hypertensive diseases.
    Keywords Other systems of medicine ; RZ201-999
    Subject code 630
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Insight into the Mechanisms Underlying the Tracheorelaxant Properties of the

    Krasniqi, Berat / Thaçi, Shpëtim / Dërmaku-Sopjani, Miribane / Rifati-Nixha, Arleta / Abazi, Sokol / Sopjani, Mentor

    Evidence-based complementary and alternative medicine : eCAM

    2020  Volume 2020, Page(s) 6510708

    Abstract: Sideritis ... ...

    Abstract Sideritis raeseri
    Language English
    Publishing date 2020-08-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171158-6
    ISSN 1741-4288 ; 1741-427X
    ISSN (online) 1741-4288
    ISSN 1741-427X
    DOI 10.1155/2020/6510708
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: JAK2-mediated Intracellular Signaling.

    Sopjani, Mentor / Morina, Rifat / Uka, Valdet / Xuan, Nguyen Thi / Dërmaku-Sopjani, Miribane

    Current molecular medicine

    2020  Volume 21, Issue 5, Page(s) 417–425

    Abstract: Janus kinase-2 (JAK2) is a non-receptor tyrosine kinase that serves key roles as the intracellular signaling effector of the cytokine receptor, such as mediating effects of leptin, erythropoietin, interferon, and growth hormone. A lot of molecular ... ...

    Abstract Janus kinase-2 (JAK2) is a non-receptor tyrosine kinase that serves key roles as the intracellular signaling effector of the cytokine receptor, such as mediating effects of leptin, erythropoietin, interferon, and growth hormone. A lot of molecular underlying mechanisms of JAK2 participation are known, however, additional signaling mechanisms of its activation, regulation, and pleiotropic signaling roles are still being explored. Here, we review the current knowledge of JAK2-mediated cellular signaling at the molecular level. In the beginning, we will focus on the recent advances in JAK2 activation and regulation. A part of our review focuses on the JAK2 involvement in various diseases/conditions. Recent advances highlight the molecular regulatory mechanisms utilized by the JAK2 signaling, thus, enabling to consider alternative therapeutic strategies to treat various diseases/conditions mediated by JAK2 by using it as a therapeutic target.
    MeSH term(s) Humans ; Janus Kinase 2/metabolism ; Signal Transduction/physiology
    Chemical Substances Janus Kinase 2 (EC 2.7.10.2)
    Language English
    Publishing date 2020-11-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2064873-X
    ISSN 1875-5666 ; 1566-5240
    ISSN (online) 1875-5666
    ISSN 1566-5240
    DOI 10.2174/1566524020666201015144702
    Database MEDical Literature Analysis and Retrieval System OnLINE

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