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  1. Article: Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets.

    Belete, Tafere Mulaw

    Annals of neurosciences

    2023  Volume 30, Issue 4, Page(s) 262–276

    Abstract: Background: Epilepsy is a chronic neurological disorder that affects approximately 50-70 million people worldwide. Epilepsy has a significant economic and social burden on patients as well as on the country. The recurrent, spontaneous seizure activity ... ...

    Abstract Background: Epilepsy is a chronic neurological disorder that affects approximately 50-70 million people worldwide. Epilepsy has a significant economic and social burden on patients as well as on the country. The recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy. The current antiepileptic drugs provide symptomatic relief by restoring the balance of excitatory and inhibitory neurotransmitters. Besides, about 30% of epileptic patients do not achieve seizure control. The prevalence of adverse drug reactions, including aggression, agitation, irritability, and associated comorbidities, is also prevalent. Therefore, researchers should focus on developing more effective, safe, and disease-modifying agents based on new molecular targets and signaling cascades.
    Summary: This review overviews several clinical trials that help identify promising new targets like lactate dehydrogenase inhibitors, c-jun n-terminal kinases, high mobility group box-1 antibodies, astrocyte reactivity inhibitors, cholesterol 24-hydroxylase inhibitors, glycogen synthase kinase-3 beta inhibitors, and glycolytic inhibitors to develop a new antiepileptic drug.
    Key messages: Approximately 30% of epileptic patients do not achieve seizure control. The current anti-seizure drugs are not disease modifying, cure or prevent epilepsy. Lactate dehydrogenase inhibitor, cholesterol 24-hydroxylase inhibitor, glycogen synthase kinase-3 beta inhibitors, and mTOR inhibitors have a promising antiepileptogenic effect.
    Language English
    Publishing date 2023-08-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2576191-2
    ISSN 0976-3260 ; 0972-7531
    ISSN (online) 0976-3260
    ISSN 0972-7531
    DOI 10.1177/09727531231185991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Recent Progress in the Development of Novel Mycobacterium Cell Wall Inhibitor to Combat Drug-Resistant Tuberculosis.

    Belete, Tafere Mulaw

    Microbiology insights

    2022  Volume 15, Page(s) 11786361221099878

    Abstract: Despite decades of research in drug development against TB, it is still the leading cause of death due to infectious diseases. The long treatment duration, patient noncompliance coupled with the ability of the tuberculosis bacilli to resist the current ... ...

    Abstract Despite decades of research in drug development against TB, it is still the leading cause of death due to infectious diseases. The long treatment duration, patient noncompliance coupled with the ability of the tuberculosis bacilli to resist the current drugs increases multidrug-resistant tuberculosis that exacerbates the situation. Identification of novel drug targets is important for the advancement of drug development against
    Language English
    Publishing date 2022-05-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2455264-1
    ISSN 1178-6361
    ISSN 1178-6361
    DOI 10.1177/11786361221099878
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  3. Article ; Online: Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer.

    Belete, Tafere Mulaw

    Drug design, development and therapy

    2022  Volume 16, Page(s) 3465–3472

    Abstract: Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens ... ...

    Abstract Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens have a narrow therapeutic index, severe adverse drug reactions, and lack metabolic stability. Besides, the metabolism of anticancer produces several non-active and toxic metabolites that reduce exposure of the target site to the parent drug. Therefore, developing better-tolerated and effective new anticancer drugs and modification of the existing anticancer drugs to minimize toxicity and increase efficacy has become a very urgent need. Deuterium incorporation reduces the metabolism of certain drugs that are breakdown by pathways involving hydrogen-carbon bond scission. For example, CYP450 mediated oxidative metabolism of drugs that involves the breakdown of a hydrogen-carbon bond affected by deuteration. Deuterium incorporation into the drug increases the half-life and reduces the dose, which provides better safety and efficacy. Deutetrabenazine is the first deuterated form of tetrabenazine approved to treat chorea associated with Huntington's disease and tardive dyskinesia. The study revealed that Deutetrabenazine has fewer neuropsychiatric side effects with favorable safety than tetrabenazine. The current review highlights the deuterium kinetic isotope effect on drug metabolism, deuterated compound pharmacokinetic property, and safety profile. Besides, this review explains the deuterated anticancer drug development update status.
    MeSH term(s) Carbon/therapeutic use ; Deuterium/chemistry ; Humans ; Huntington Disease/drug therapy ; Neoplasms/drug therapy ; Tardive Dyskinesia/drug therapy ; Tetrabenazine/adverse effects
    Chemical Substances Carbon (7440-44-0) ; Deuterium (AR09D82C7G) ; Tetrabenazine (Z9O08YRN8O)
    Language English
    Publishing date 2022-10-04
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2451346-5
    ISSN 1177-8881 ; 1177-8881
    ISSN (online) 1177-8881
    ISSN 1177-8881
    DOI 10.2147/DDDT.S379496
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Current Status of Gene Therapy for the Treatment of Cancer.

    Belete, Tafere Mulaw

    Biologics : targets & therapy

    2021  Volume 15, Page(s) 67–77

    Abstract: Gene therapy is the administration of foreign genomic material into the host tissue to modify the expression of a gene product or to change the biological properties of cells for therapeutic use. Initially, the major objective of gene therapy was to ... ...

    Abstract Gene therapy is the administration of foreign genomic material into the host tissue to modify the expression of a gene product or to change the biological properties of cells for therapeutic use. Initially, the major objective of gene therapy was to manage genetic diseases, but now different disorders with several patterns of acquired and inherited disorders are targets of gene therapy. Over three decades, the advancement of Genome engineering technologies facilitated gene therapy for the prevention and management of intractable diseases. Researchers are advancing with cautious optimism that safe and effective treatment will give to patients with single-gene disorders and complex acquired disorders. To date, over 3000 genes associates with disease-causing mutations, and about 2600 gene therapy trials are undergoing for the management of various disorders. This review summarizes the principles of genome-editing approaches, such as zinc finger nucleases, transcription activator-like effector nucleases, meganucleases, and the CRISPR/Cas9 system with the underlying mechanisms. This review also explains the types of gene delivery systems as viral [adenoviral, adeno association, herpes simplex virus] and nonviral delivery systems (physical: DNA bombardment, electroporation) and (chemical: Cationic lipids, cationic polymers). Finally, this review summarizes gene therapy medicines approved to treat cancer in detail, including names, indications, vectors, and mode of gene therapy. Gene therapy becomes an alternative to an existing management for different diseases. Therefore, gene products with safe vectors and better biotechnologies play a significant role in the prophylaxis and management of various disorders in the future.
    Language English
    Publishing date 2021-03-18
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2415708-9
    ISSN 1177-5491 ; 1177-5475
    ISSN (online) 1177-5491
    ISSN 1177-5475
    DOI 10.2147/BTT.S302095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Review on Up-to-Date Status of Candidate Vaccines for COVID-19 Disease.

    Belete, Tafere Mulaw

    Infection and drug resistance

    2021  Volume 14, Page(s) 151–161

    Abstract: The global pandemic of COVID-19 caused by SARS-CoV-2 continues to spread and poses serious threats to public health and economic stability throughout the world. Thus, to protect the global population, developing safe and effective vaccines is mandatory ... ...

    Abstract The global pandemic of COVID-19 caused by SARS-CoV-2 continues to spread and poses serious threats to public health and economic stability throughout the world. Thus, to protect the global population, developing safe and effective vaccines is mandatory to control the spread of SARS-CoV-2 pandemic. Since genomic sequences of SARS-CoV-2 and SARS-CoV-1 have similarity and use the same receptor (ACE2), it is important to learn from the development of SARS-CoV-1 vaccines for the development of SARS-CoV-2 vaccines. Normally vaccine development takes 10-15 years but vaccine development against SARS-CoV2 is going on at a very fast pace resulting in almost breakthrough methods of vaccine development by several research institutions. The whole process of vaccine development including clinical trials gets shortened and may be fast tracked to 15-18 months. Global collaborations and increased research efforts among the scientific community have led to more than 214 candidate vaccines globally. The current review highlights the different approaches and technologies used around the world for the design and development of the vaccines and also focuses on the recent status of the SARS-CoV-2 vaccine candidates under development by various institutions to combat the world threat of COVID-19 pandemic.
    Language English
    Publishing date 2021-01-19
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2494856-1
    ISSN 1178-6973
    ISSN 1178-6973
    DOI 10.2147/IDR.S288877
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: An Up-to-Date Overview of Therapeutic Agents for the Treatment of COVID-19 Disease.

    Mulaw Belete, Tafere

    Clinical pharmacology : advances and applications

    2020  Volume 12, Page(s) 203–212

    Abstract: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven ... ...

    Abstract Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven effective drugs or vaccines are available for the management of COVID-19 disease. The pace of normal drug development progression is unacceptable in the context of the current pandemic. Therefore, repurposing the existing drugs that were used for the treatment of malaria, Ebola, and influenza helps rapid drug development for COVID-19. Currently, several repurposing candidate drugs are in a clinical trial including, chloroquine monoclonal antibodies, convalescent plasma, interferon, and antiviral therapies. Antiviral drugs like arbidol, remdesiv and favirnavir are the most promising due to the similarities of the viruses regarding viral entry, fusion, uncoating, and replication. This review article provides an overview of the potential therapeutic agent, which displayed better clinical treatment outcomes. Moreover, with further understanding of the SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise, and investigations on these novels anti-SARSCoV- 2 agents are also reviewed.
    Language English
    Publishing date 2020-12-14
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2520726-X
    ISSN 1179-1438
    ISSN 1179-1438
    DOI 10.2147/CPAA.S284809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Recent Progress in the Development of New Antimalarial Drugs with Novel Targets.

    Belete, Tafere Mulaw

    Drug design, development and therapy

    2020  Volume 14, Page(s) 3875–3889

    Abstract: Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria ... ...

    Abstract Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases,
    MeSH term(s) Animals ; Antimalarials/chemical synthesis ; Antimalarials/chemistry ; Antimalarials/pharmacology ; Drug Development ; Humans ; Malaria/drug therapy ; Parasitic Sensitivity Tests ; Plasmodium falciparum/drug effects
    Chemical Substances Antimalarials
    Language English
    Publishing date 2020-09-22
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2451346-5
    ISSN 1177-8881 ; 1177-8881
    ISSN (online) 1177-8881
    ISSN 1177-8881
    DOI 10.2147/DDDT.S265602
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A Recent Achievement In the Discovery and Development of Novel Targets for the Treatment of Type-2 Diabetes Mellitus.

    Belete, Tafere Mulaw

    Journal of experimental pharmacology

    2020  Volume 12, Page(s) 1–15

    Abstract: Type 2 diabetes (T2DM) is a chronic metabolic disorder. Impaired insulin secretion, enhanced hepatic glucose production, and suppressed peripheral glucose use are the main defects responsible for developing the disease. Besides, the pathophysiology of ... ...

    Abstract Type 2 diabetes (T2DM) is a chronic metabolic disorder. Impaired insulin secretion, enhanced hepatic glucose production, and suppressed peripheral glucose use are the main defects responsible for developing the disease. Besides, the pathophysiology of T2DM also includes enhanced glucagon secretion, decreased incretin secretion, increased renal glucose reabsorption, and adipocyte, and brain insulin resistance. The increasing prevalence of T2DM in the world beseeches an urgent need for better treatment options. The antidiabetic drugs focus on control of blood glucose concentration, but the future treatment goal is to delay disease progression and treatment failure, which causes poorer glycemic regulation. Recent treatment approaches target on several novel pathophysiological defects present in T2DM. Some of the promising novel targets being under clinical development include those that increase insulin sensitization (antagonists of glucocorticoids receptor), decreasing hepatic glucose production (glucagon receptor antagonist, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase). This review summarizes studies that are available on novel targets being studied to treat T2DM with an emphasis on the small molecule drug design. The experience gathered from earlier studies and knowledge of T2DM pathways can guide the anti-diabetic drug development toward the discovery of drugs essential to treat T2DM.
    Language English
    Publishing date 2020-01-10
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2587465-2
    ISSN 1179-1454
    ISSN 1179-1454
    DOI 10.2147/JEP.S226113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: A review on Promising vaccine development progress for COVID-19 disease.

    Belete, Tafere Mulaw

    Vacunas

    2020  Volume 21, Issue 2, Page(s) 121–128

    Abstract: The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. ...

    Abstract The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. Despite several measures undertaken, the spread of this virus is ongoing. So far, more than 1,560,000 cases and 1000,000 deaths occurred in the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS. However, currently, no approved vaccine exists for these coronavirus strains. Such Previous research efforts to develop a coronavirus vaccine in the years following the 2003 pandemic have opened the door for the scientist to design a new vaccine for the COVID-19. Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor. By using different vaccine development platforms including whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines several candidates displayed efficacy in vitro studies but few progressed to clinical trials. This review provides a brief introduction of the general features of SARS-CoV-2 and discusses the current progress of ongoing advances in designing vaccine development efforts to counter COVID-19.
    Keywords covid19
    Language English
    Publishing date 2020-06-13
    Publishing country Spain
    Document type Journal Article ; Review
    ISSN 1576-9887
    ISSN 1576-9887
    DOI 10.1016/j.vacun.2020.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Evaluation of Wound Healing and Anti-Inflammatory Activities of 80% Methanol Crude Extract and Solvent Fractions of

    Shewaye, Daniel Gizachew / Kahaliw, Wubayehu / Mulaw Belete, Tafere / Ahmed, Nejat

    Evidence-based complementary and alternative medicine : eCAM

    2023  Volume 2023, Page(s) 9980866

    Abstract: Introduction: The leaves of : Objective: This study aimed to evaluate wound healing and anti-inflammatory activity of 80% methanol crude extract and solvent fractions of : Method: The leaves of : Result: Both acute dermal and oral toxicity ... ...

    Abstract Introduction: The leaves of
    Objective: This study aimed to evaluate wound healing and anti-inflammatory activity of 80% methanol crude extract and solvent fractions of
    Method: The leaves of
    Result: Both acute dermal and oral toxicity tests were found to be safe after topical application of 2000 mg/kg of 10% (w/w) CEO and oral administration of 2000 mg/kg of crude extract suspension, respectively. Both 5% and 10% (w/w) CEO produced significant (
    Conclusion: The increase in wound contraction, reduction in period of epithelialization, and increase in tensile strength support the traditional claims of
    Language English
    Publishing date 2023-01-19
    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 10.1155/2023/9980866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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