Gazi University

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Big data is a term for massive data sets having large, more varied and complex structure with the difficulties of storing, analyzing and visualizing for further processes or results. The process of research into massive amounts of data to reveal hidden patterns and secret correlations named as big data analytics. These useful informations for companies or organizations with the help of gaining richer and deeper insights and getting an advantage over the competition. For this reason, big data implementations need to be analyzed and executed as accurately as possible. This paper presents an overview of big data's content, scope, samples, methods, advantages and challenges and discusses privacy concern on it.

Turmeric (Curcuma longa) is a type of herb belonging to ginger family, which is widely grown in southern and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran, Malesia, India, China, Polynesia, and Thailand, is often used as spice and has an effect on the nature, color, and taste of foods. Turmeric is also known to have been used for centuries in India and China for the medical treatments of illnesses such as dermatologic diseases, infection, stress, and depression. Turmeric's effects on health are generally centered upon an orange-yellow colored, lipophilic polyphenol substance called "curcumin," which is acquired from the rhizomes of the herb. Curcumin is known recently to have antioxidant, anti-inflammatory, anticancer effects and, thanks to these effects, to have an important role in prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological, cardiovascular diseases, and diabetic. Furthermore, it is aimed to increase the biological activity and physiological effects of the curcumin on the body by synthesizing curcumin analogues. This article reviews the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological activities, and effects on health of curcumin.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) belongs to polyphenols' stilbenoids group, possessing two phenol rings linked to each other by an ethylene bridge. This natural polyphenol has been detected in more than 70 plant species, especially in grapes' skin and seeds, and was found in discrete amounts in red wines and various human foods. It is a phytoalexin that acts against pathogens, including bacteria and fungi. As a natural food ingredient, numerous studies have demonstrated that resveratrol possesses a very high antioxidant potential. Resveratrol also exhibit antitumor activity, and is considered a potential candidate for prevention and treatment of several types of cancer. Indeed, resveratrol anticancer properties have been confirmed by many in vitro and in vivo studies, which shows that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression). Even more, other bioactive effects, namely as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. Nonetheless, resveratrol application is still being a major challenge for pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects. In this sense, this review summarized current data on resveratrol pharmacological effects.

Many food-derived phytochemicals and their derivatives represent a cornucopia of new anti-cancer compounds. Luteolin (3,4,5,7-tetrahydroxy flavone) is a flavonoid found in different plants such as vegetables, medicinal herbs, and fruits. It acts as an anticancer agent against various types of human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers. It also blocks cancer development in vitro and in vivo by inhibition of proliferation of tumor cells, protection from carcinogenic stimuli, and activation of cell cycle arrest, and by inducing apoptosis through different signaling pathways. Luteolin can additionally reverse epithelial-mesenchymal transition (EMT) through a mechanism that involves cytoskeleton shrinkage, induction of the epithelial biomarker E-cadherin expression, and by down-regulation of the mesenchymal biomarkers N-cadherin, snail, and vimentin. Furthermore, luteolin increases levels of intracellular reactive oxygen species (ROS) by activation of lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells, and by activation of ER stress-associated proteins expressions, including phosphorylation of eIF2α, PERK, CHOP, ATF4, and cleaved-caspase 12. Accordingly, the present review article summarizes the progress of recent research on luteolin against several human cancers.

In the past, the beneficial effects of fermented foods on health were unknown, and so people primarily used fermentation to preserve foods, enhance shelf life, and improve flavour. Fermented foods became an important part of the diet in many cultures, and over time fermentation has been associated with many health benefits. Because of this, the fermentation process and the resulting fermented products have recently attracted scientific interest. In addition, microorganisms contributing to the fermentation process have recently been associated with many health benefits, and so these microorganisms have become another focus of attention. Lactic acid bacteria (LAB) have been some of the most studied microorganisms. During fermentation, these bacteria synthesize vitamins and minerals, produce biologically active peptides with enzymes such as proteinase and peptidase, and remove some non-nutrients. Compounds known as biologically active peptides, which are produced by the bacteria responsible for fermentation, are also well known for their health benefits. Among these peptides, conjugated linoleic acids (CLA) have a blood pressure lowering effect, exopolysaccharides exhibit prebiotic properties, bacteriocins show anti-microbial effects, sphingolipids have anti-carcinogenic and anti-microbial properties, and bioactive peptides exhibit anti-oxidant, anti-microbial, opioid antagonist, anti-allergenic, and blood pressure lowering effects. As a result, fermented foods provide many health benefits such as anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic and anti-atherosclerotic activity. However, some studies have shown no relationship between fermented foods and health benefits. Therefore, this paper aims to investigate the health effects of fermented foods.

By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to the Lamiaceae, Lauraceae, Myrtaceae, and Myristicaceae families. It is one of the major constituents of clove (Syzygium aromaticum (L.) Merr. & L.M. Perry, Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens.

Metric learning aims to measure the similarity among samples while using an optimal distance metric for learning tasks. Metric learning methods, which generally use a linear projection, are limited in solving real-world problems demonstrating non-linear characteristics. Kernel approaches are utilized in metric learning to address this problem. In recent years, deep metric learning, which provides a better solution for nonlinear data through activation functions, has attracted researchers’ attention in many different areas. This article aims to reveal the importance of deep metric learning and the problems dealt with in this field in the light of recent studies. As far as the research conducted in this field are concerned, most existing studies that are inspired by Siamese and Triplet networks are commonly used to correlate among samples while using shared weights in deep metric learning. The success of these networks is based on their capacity to understand the similarity relationship among samples. Moreover, sampling strategy, appropriate distance metric, and the structure of the network are the challenging factors for researchers to improve the performance of the network model. This article is considered to be important, as it is the first comprehensive study in which these factors are systematically analyzed and evaluated as a whole and supported by comparing the quantitative results of the methods.

α- and β-pinene are well-known representatives of the monoterpenes group, and are found in many plants’ essential oils. A wide range of pharmacological activities have been reported, including antibiotic resistance modulation, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, anti-inflammatory, anti-Leishmania, and analgesic effects. This article aims to summarize the most prominent effects of α- and β-pinene, namely their cytogenetic, gastroprotective, anxiolytic, cytoprotective, anticonvulsant, and neuroprotective effects, as well as their effects against H2O2-stimulated oxidative stress, pancreatitis, stress-stimulated hyperthermia, and pulpal pain. Finally, we will also discuss the bioavailability, administration, as well as their biological activity and clinical applications.

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

OBJECTIVE: Some natural products consisting of the alkaloids yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type); the flavonoid derivatives quercetin, apigenin, genistein, naringin, silymarin, and silibinin; and the phenolic acids namely gallic acid, caffeic acid, chlorogenic acid, and quinic acid, were tested for their in vitro antiviral, antibacterial, and antifungal activities and cytotoxicity. MATERIALS AND METHODS: Antiviral activity of the compounds was tested against DNA virus herpes simplex type 1 and RNA virus parainfluenza (type-3). Cytotoxicity of the compounds was determined using Madin-Darby bovine kidney and Vero cell lines, and their cytopathogenic effects were expressed as maximum non-toxic concentration. Antibacterial activity was assayed against following bacteria and their isolated strains: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis, although they were screened by microdilution method against two fungi: Candida albicans and Candida parapsilosis. RESULTS: Atropine and gallic acid showed potent antiviral effect at the therapeutic range of 0.8-0.05 µg ml(-1), whilst all of the compounds exerted robust antibacterial effect. CONCLUSION: Antiviral and antimicrobial effects of the compounds tested herein may constitute a preliminary step for further relevant studies to identify the mechanism of action.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. METHODS: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. FINDINGS: =59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). INTERPRETATION: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. FUNDING: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.

An asymptotic interation method for solving second-order homogeneous linear differential equations of the form y'' = lambda(x) y' + s(x) y is introduced, where lambda(x) \neq 0 and s(x) are C-infinity functions. Applications to Schroedinger type problems, including some with highly singular potentials, are presented.

BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The initial assay of mutant α-galactosidase forms that we used to categorize 67 patients with Fabry's disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant α-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (≥50% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS: The primary end-point analysis, involving patients with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy, did not show a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline in the estimated glomerular filtration rate (GFR) and measured GFR were -0.30±0.66 and -1.51±1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left-ventricular-mass index decreased significantly from baseline (-7.7 g per square meter; 95% confidence interval [CI], -15.4 to -0.01), particularly when left ventricular hypertrophy was present (-18.6 g per square meter; 95% CI, -38.2 to 1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS: Among all randomly assigned patients (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study AT1001-041].).

Two-particle correlations in relative azimuthal angle ($\ensuremath{\Delta}\ensuremath{\phi}$) and pseudorapidity ($\ensuremath{\Delta}\ensuremath{\eta}$) are measured in $\sqrt{{s}_{\mathrm{NN}}}=5.02\text{ }\text{ }\mathrm{TeV}$ $p+\mathrm{Pb}$ collisions using the ATLAS detector at the LHC. The measurements are performed using approximately $1\text{ }\text{ }\ensuremath{\mu}{\mathrm{b}}^{\ensuremath{-}1}$ of data as a function of transverse momentum (${p}_{\mathrm{T}}$) and the transverse energy ($\ensuremath{\Sigma}{E}_{\mathrm{T}}^{\mathrm{Pb}}$) summed over $3.1&lt;\ensuremath{\eta}&lt;4.9$ in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range ($2&lt;|\ensuremath{\Delta}\ensuremath{\eta}|&lt;5$) ``near-side'' ($\ensuremath{\Delta}\ensuremath{\phi}\ensuremath{\sim}0$) correlation that grows rapidly with increasing $\ensuremath{\Sigma}{E}_{\mathrm{T}}^{\mathrm{Pb}}$. A long-range ``away-side'' ($\ensuremath{\Delta}\ensuremath{\phi}\ensuremath{\sim}\ensuremath{\pi}$) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small $\ensuremath{\Sigma}{E}_{\mathrm{T}}^{\mathrm{Pb}}$, is found to match the near-side correlation in magnitude, shape (in $\ensuremath{\Delta}\ensuremath{\eta}$ and $\ensuremath{\Delta}\ensuremath{\phi}$) and $\ensuremath{\Sigma}{E}_{\mathrm{T}}^{\mathrm{Pb}}$ dependence. The resultant $\ensuremath{\Delta}\ensuremath{\phi}$ correlation is approximately symmetric about $\ensuremath{\pi}/2$, and is consistent with a dominant $\mathrm{cos}2\ensuremath{\Delta}\ensuremath{\phi}$ modulation for all $\ensuremath{\Sigma}{E}_{\mathrm{T}}^{\mathrm{Pb}}$ ranges and particle ${p}_{\mathrm{T}}$.

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer's disease and its potential as a lead compound in clinical applications.

Trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in Africa, Asia, and South America. In a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a Turkish plant. Here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their in vitro activities against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani. The cytotoxicities of more than 100 compounds for mammalian L6 cells were also assessed and compared to their antiparasitic activities. Several compounds were investigated in vivo for their antileishmanial and antitrypanosomal efficacies in mouse models. Overall, the best in vitro trypanocidal activity for T. brucei rhodesiense was exerted by 7,8-dihydroxyflavone (50% inhibitory concentration [IC50], 68 ng/ml), followed by 3-hydroxyflavone, rhamnetin, and 7,8,3',4'-tetrahydroxyflavone (IC50s, 0.5 microg/ml) and catechol (IC50, 0.8 microg/ml). The activity against T. cruzi was moderate, and only chrysin dimethylether and 3-hydroxydaidzein had IC50s less than 5.0 microg/ml. The majority of the metabolites tested possessed remarkable leishmanicidal potential. Fisetin, 3-hydroxyflavone, luteolin, and quercetin were the most potent, giving IC50s of 0.6, 0.7, 0.8, and 1.0 microg/ml, respectively. 7,8-Dihydroxyflavone and quercetin appeared to ameliorate parasitic infections in mouse models. Generally, the test compounds lacked cytotoxicity in vitro and in vivo. By screening a large number of flavonoids and analogues, we were able to establish some general trends with respect to the structure-activity relationship, but it was not possible to draw clear and detailed quantitative structure-activity relationships for any of the bioactivities by two different approaches. However, our results can help in directing the rational design of 7,8-dihydroxyflavone and quercetin derivatives as potent and effective antiprotozoal agents.

In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.