Therapeutic Options for Treatment of COVID-19: A Review from Repur-posed Drugs to New Drug Targets

2020 ◽  
Vol 21 ◽  
Author(s):  
Bushra Akhtar ◽  
Faqir Muhammad ◽  
Ali Sharif ◽  
Abdul Hannan
Keyword(s):  
Drug Targets ◽  
Research Work ◽  
Daily Routine ◽  
Clinical Tests ◽  
Rapid Pace ◽  
Effect Duration ◽  
Repurposed Drugs ◽  
Day By Day

Abstract: A new virus pandemic, COVID-19, has instigated substantial damage to human wellness in terms of death and ailment, economic compromises along with restriction of daily routine life. There is a profound increase in the number of victims and causalities day by day. Thus far, there is no available treatment and vaccination for COVID-19. Under the rapid pace of clinical research work, scientists have reported different drugs having in vitro efficacy against COVID-19. But the evidences for their in vivo use have not been established yet in terms of clinical effect, duration of stay in intensive care units as well as the refuge of these drugs and their combinations. Anti-retroviral, Remdesivir, as well as different repurposed drugs like chloroquine and hydroxychloroquine have shown promising effects in vitro. Numerous clinical tests are underway in order to explore the benefits of these drugs. This review covers the disease pathogenesis and various potential targets with reference to the virulence of COVID-19.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli
Keyword(s):  
Drug Targets ◽  
Redox Homeostasis ◽  
Cost Effective ◽  
Structural Features ◽  
Mammalian Host ◽  
Neglected Diseases ◽  
Nitrogen Compounds ◽  
Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

Nyctanthes Arbor-Tristis and its Role in the Alleviation of Arthritic Pain: A Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1147-1156
Author(s):  
Ruchi Singh ◽  
Syed M. Hasan ◽  
Amit Verma ◽  
Sanjay K. Panda
Keyword(s):  
Research Work ◽  
Plant Distribution ◽  
Pharmacological Activities ◽  
Whole Plant ◽  
Modern Drug ◽  
Active Chemical ◽  
Drug Synthesis ◽  
New Compounds

Background: A plant is a reservoir of potentially useful active chemical entities which act as drugs as well as intermediates for the discovery of newer molecules and provide newer leads for modern drug synthesis. The demand for new compounds in the field of medicine and biotechnology is centuries old and with a rise in chronic diseases and resistance to existing drugs in the field of anti-infective agents, the chemicals obtained from plant sources have been an area of attraction. The whole plant has possessed multiple pharmacological activities. This is scientifically established by in-vivo and in-vitro studies. Methods: Various electronic databases such as PubMed, Science Direct, Scopus and Google were searched to collect the data of the present review. All the collected information is categorized into different sections as per the aim of the paper. Results: Fifty-six research and review papers have been studied and were included in this review article. After a detailed study, we provide a significant description of various phytochemicals present in Nyctanthes arbor-tristis Linn., which is responsible for various pharmacological activities. Twenty of studied articles gives a general introduction and ethnobotanical information about the plant, two papers contained microscopic detail of leaf and fruit. Twenty papers contained information about the phytoconstituents present in different parts of Nyctanthes arbor-tristis plant and fourteen articles reported pharmacological activities like antioxidant, anti-inflammatory, antiarthritic, antimicrobial and immunobiotic activity. Conclusion: This review explores the published research work comprising the ethnobotanical description of the subjected plant, distribution, phytochemical profile, and arthritis-related pharmacological activities.

scholarly journals Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma

2021 ◽  
Author(s):  
Yu-bo Zhou ◽  
Yang-ming Zhang ◽  
Hong-hui Huang ◽  
Li-jing Shen ◽  
Xiao-feng Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Targets ◽  
Single Agent ◽  
Hdac Inhibitors ◽  
Preclinical Study ◽  
Parp Cleavage ◽  
Rpmi 8226 ◽  
Ongoing Phase

AbstractHDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%–35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.

scholarly journals Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hu Lei ◽  
Han-Zhang Xu ◽  
Hui-Zhuang Shan ◽  
Meng Liu ◽  
Ying Lu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Progenitor Cells ◽  
Chronic Myelogenous Leukemia ◽  
Drug Targets ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Tki Resistance

AbstractIdentifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABLT315I-induced CML in mice with the reduction of Lin−Sca1+c-Kit+ CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.

scholarly journals Numerical Investigation of Ferrofluid Preparation during In-Vitro Culture of Cancer Therapy for Magnetic Nanoparticle Hyperthermia

Sensors ◽  
2021 ◽  
Vol 21 (16) ◽  
pp. 5545 ◽  
Author(s):  
Izaz Raouf ◽  
Piotr Gas ◽  
Heung Soo Kim
Keyword(s):  
Numerical Model ◽  
Cancer Therapy ◽  
Magnetic Nanoparticle ◽  
Research Work ◽  
Thermal Response ◽  
Linear Response Theory ◽  
Novel Approach ◽  
Magnetic Nanoparticle Hyperthermia

Recently, in-vitro studies of magnetic nanoparticle (MNP) hyperthermia have attracted significant attention because of the severity of this cancer therapy for in-vivo culture. Accurate temperature evaluation is one of the key challenges of MNP hyperthermia. Hence, numerical studies play a crucial role in evaluating the thermal behavior of ferrofluids. As a result, the optimum therapeutic conditions can be achieved. The presented research work aims to develop a comprehensive numerical model that directly correlates the MNP hyperthermia parameters to the thermal response of the in-vitro model using optimization through linear response theory (LRT). For that purpose, the ferrofluid solution is evaluated based on various parameters, and the temperature distribution of the system is estimated in space and time. Consequently, the optimum conditions for the ferrofluid preparation are estimated based on experimental and mathematical findings. The reliability of the presented model is evaluated via the correlation analysis between magnetic and calorimetric methods for the specific loss power (SLP) and intrinsic loss power (ILP) calculations. Besides, the presented numerical model is verified with our experimental setup. In summary, the proposed model offers a novel approach to investigate the thermal diffusion of a non-adiabatic ferrofluid sample intended for MNP hyperthermia in cancer treatment.

scholarly journals Mammalian deubiquitinating enzyme inhibitors display in vitro and in vivo activity against malaria parasites and potentiate artemisinin action

2020 ◽  
Author(s):  
Nelson V. Simwela ◽  
Katie R. Hughes ◽  
Michael T. Rennie ◽  
Michael P. Barrett ◽  
Andrew P. Waters
Keyword(s):  
Anticancer Agents ◽  
Drug Targets ◽  
Reverse Genetics ◽  
Enzyme Inhibitors ◽  
Artemisinin Resistance ◽  
Drug Repurposing ◽  
Antimalarial Drugs ◽  
Malaria Parasites

AbstractCurrent malaria control efforts rely significantly on artemisinin combinational therapies which have played massive roles in alleviating the global burden of the disease. Emergence of resistance to artemisinins is therefore, not just alarming but requires immediate intervention points such as development of new antimalarial drugs or improvement of the current drugs through adjuvant or combination therapies. Artemisinin resistance is primarily conferred by Kelch13 propeller mutations which are phenotypically characterised by generalised growth quiescence, altered haemoglobin trafficking and downstream enhanced activity of the parasite stress pathways through the ubiquitin proteasome system (UPS). Previous work on artemisinin resistance selection in a rodent model of malaria, which we and others have recently validated using reverse genetics, has also shown that mutations in deubiquitinating enzymes, DUBs (upstream UPS component) modulates susceptibility of malaria parasites to both artemisinin and chloroquine. The UPS or upstream protein trafficking pathways have, therefore, been proposed to be not just potential drug targets, but also possible intervention points to overcome artemisinin resistance. Here we report the activity of small molecule inhibitors targeting mammalian DUBs in malaria parasites. We show that generic DUB inhibitors can block intraerythrocytic development of malaria parasites in vitro and possess antiparasitic activity in vivo and can be used in combination with additive effect. We also show that inhibition of these upstream components of the UPS can potentiate the activity of artemisinin in vitro as well as in vivo to the extent that ART resistance can be overcome. Combinations of DUB inhibitors anticipated to target different DUB activities and downstream 20s proteasome inhibitors are even more effective at improving the potency of artemisinins than either inhibitors alone providing proof that targeting multiple UPS activities simultaneously could be an attractive approach to overcoming artemisinin resistance. These data further validate the parasite UPS as a target to both enhance artemisinin action and potentially overcome resistance. Lastly, we confirm that DUB inhibitors can be developed into in vivo antimalarial drugs with promise for activity against all of human malaria and could thus further exploit their current pursuit as anticancer agents in rapid drug repurposing programs.Graphical abstract

scholarly journals Imbir i czosnek – surowce roślinne obniżające poziom cholesterolu i glukozy

2020 ◽  
Vol 21 (3) ◽  
Author(s):  
Małgorzata Kania-Dobrowolska ◽  
Justyna Baraniak ◽  
Aleksandra Górska ◽  
Marlena Wolek ◽  
Anna Bogacz
Keyword(s):  
Type Ii Diabetes ◽  
Processed Food ◽  
Clinical Tests ◽  
Cholesterol Levels ◽  
Elevated Glucose ◽  
Unbalanced Diet ◽  
Lifestyle Diseases

Atherosclerosis and type II diabetes can be classified as lifestyle diseases. Unbalanced diet (highly processed food, excess salt food), a sedentary lifestyle and the use of stimulants (cigarettes, alcohol) can contribute to the emergence of both diseases. Both these diseases can coexist simultaneously. The development of type 2 diabetes may accelerate the development of atherosclerotic plaque, which in turn leads to many organ complications as well as death. People with slightly elevated glucose and cholesterol levels can be advised to take natural plant ingredients such as garlic and ginger along with changing their diet and increasing physical activity. garlic and ginger can be consumed alone as well as an addition to many dishes. In vitro and in vivo and clinical tests indicate the possibility of supporting the regulation of blood glucose and cholesterol levels by adding garlic and ginger to the diet.

scholarly journals Development, Optimisation and Evaluation of Ketoprofen Lipospheres

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1853-1863
Author(s):  
Shubhra Rai ◽  
Gopal Rai ◽  
Ashish Budhrani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Research Work ◽  
Extended Period ◽  
Entrapment Efficiency ◽  
Inflammatory Activity ◽  
Scanning Calorimetry ◽  
Anti Inflammatory

Lipospheres represent a novel type of fat-based encapsulation system produced for the topical drug delivery of bioactive compounds. The goal of this research work was to develop lipospheres, including ketoprofen applied for topical skin drug delivery. Ketoprofen lipospheres were formulated by melt emulsification method using stearic acid and Phospholipon® 90G. The lipospheres were analysed in terms of particle size and morphology, entrapment efficiency, Differential scanning calorimetry, In-vitro drug release, In-vivo (Anti-inflammatory activity). Outcomes of research revealed that particle size was found to be 9.66 µm and entrapment efficiency 86.21 ± 5.79 %. In-vivo, the study of ketoprofen loaded lipospheres formulation shows a higher plain formulation concentration in plasma (5.61 mg/mL). For dermis, ketoprofen retention was 27.02 ± 5.4 mg/mL for the lipospheres formulation, in contrast to that of the plain formulation group (10.05 ± 2.8 mg/mL). The anti-inflammatory effect of liposphere drug delivery systems was assessed by the xylene induced ear oedema technique and compared with marketed products. Finally, it seems that the liposphere drug delivery system possesses superior anti-inflammatory activity as compared to the marketed product gel consistencies. Liposphere may be capable of entrapping the medicament at very high levels and controlling its release over an extended period. Liposphere furnishes a proper size for topical delivery as well as is based on non-irritating and non-toxic lipids; it’s a better option for application on damaged or inflamed skin.

scholarly journals An In-Silico Study on Selected Organosulfur Compounds as Potential Drugs for SARS-CoV-2 Infection via Binding Multiple Drug Targets

2020 ◽  
Author(s):  
Liya Thurakkal ◽  
Satyam Singh ◽  
Sushabhan Sadhukhan ◽  
Mintu Porel
Keyword(s):  
Drug Targets ◽  
Target Prediction ◽  
Multiple Drug ◽  
Organosulfur Compounds ◽  
Potential Candidate ◽  
Health Crisis ◽  
Drug Molecules ◽  
Main Protease

The emerging paradigm shift from ‘one molecule, one target, for one disease’ towards ‘multi-targeted small molecules’ has paved an ingenious pathway in drug discovery in recent years. This idea has been extracted for the investigation of competent drug molecules for the unprecedented COVID-19 pandemic which became the greatest global health crisis now. Perceiving the importance of organosulfur compounds against SARS-CoV-2 from the drugs under clinical trials, a class of organosulfur compounds effective against SARS-CoV were selected and studied the interaction with multiple proteins of the SARS-CoV-2. One compound displayed inhibition against five proteins (both structural and non-structural) of the virus namely, main protease, papain-like protease, spike protein, helicase and RNA dependent RNA polymerase. Consequently, this compound emanates as a potential candidate for treating the virulent disease. The pharmacokinetics, ADMET properties and target prediction studies carried out in this work further inflamed the versatility of the compound and urge to execute <i>in-vitro</i> and <i>in-vivo</i> analysis on SARS-CoV-2 in the future.<br>

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