The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and α-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.

Artemisinin-based Combination Therapies (ACTs) are currently the frontline treatment against Plasmodium falciparum malaria, but parasite resistance to artemisinin (ART) and its derivatives, core components of ACTs, is spreading in the Mekong countries. In this study, we report the synthesis of several novel artemisinin derivatives and evaluate their in vitro and in silico capacity to counteract Plasmodium falciparum artemisinin resistance. Furthermore, recognizing that the malaria parasite devotes considerable resources to minimizing the oxidative stress that it creates during its rapid consumption of hemoglobin and the release of heme, we sought to explore whether further augmentation of this oxidative toxicity might constitute an important addition to artemisinins. The present report demonstrates, in vitro, that FM-AZ, a newly synthesized artemisinin derivative, has a lower IC50 than artemisinin in P. falciparum and a rapid action in killing the parasites. The docking studies for important parasite protein targets, PfATP6 and PfHDP, complemented the in vitro results, explaining the superior IC50 values of FM-AZ in comparison with ART obtained for the ART-resistant strain. However, cross-resistance between FM-AZ and artemisinins was evidenced in vitro.

BackgroundAlzheimer’s disease (AD) accounts for 60‐70% of dementia cases. It is a multi‐factorial process and not all factors that affect its appearance and development have been clarified. Several parasites have been correlated with dementia [1] and development of AD has been associated with Toxoplasma gondii parasitism [2].In the present study, IgG and IgM antibodies against Ascaris Lumbricoides (AL) antigens were detected in the serum of 60 patients with mild, medium and severe AD, 20 from each group.MethodsAntigens of AL were adhered to the bottom of ELISA plate (IBL International GMBH) in order to measure the level of IgG and IgM antibodies. Peroxidase labelled Protein A or goat anti‐human IgM were used to bind IgG and IgM antibodies, respectively.ResultsAccording to the results, 30% of patients with severe AD were positive to IgG antibodies (Ab) against AL antigens (Ab concentration > 9 U/µL) whereas none of the patients with mild and moderate AD was positive (Figures 1, 2). The mean IgG Ab concentration in this group was 2.1 times higher than the mean value of patients with mild and moderate AD (p = 0.001 according to t‐test). Additionally, 35% of patients with severe AD were positive to IgM Abs while 16.7% and 8% of IgM positive samples were found in patients with mild and moderate disease.ConclusionThe results present a potential correlation of Ascaris lumbricoides infection and antibodies development with Alzheimer’s Disease.References: [1] Gislaine Cristina Lopes Machado‐Porto etal., Reversible dementia due to neurocysticercosis: Improvement of the racemose type with antihistamines, Dement Neuropsychol, 2015; 9(1): 85‐90. [2] Hossein Mahmoudvand etal., Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer’s Disease in the BALB/c Mice. J Parasitol (2016); 102 (6): 629‐635.

Background: Neuroinflammation plays an essential role in the advancement of both Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD). Polyunsaturated fatty acids and their oxidized metabolites, in particular the bioactive oxylipins, are multifunctional molecules involved in the regulation and resolution of inflammation. The relationships between oxylipins, AD and SIVD remain to be clarified. Methods:The present study applied a targeted lipidomics platform to quantitatively probe for 72 oxylipins in AD (n¼30) and non-AD (n¼54) participants, including strata of extensive (n¼43, SIVD) or minimal (n¼41, Non-SIVD) white matter hyperintensities (WMHs). WMHs were identified through multimodal MRI, and quantified using a personalized semi-automatic processing pipeline (Lesion Explorer). The oxylipins were extracted from serum using solid phase extraction, and quantified with UPLC-MS/MS. Executive function was assessed using the Stroop and Trail-Making B (TMT-B) tests. Results: In a multivariate analysis of covariance model controlling for age and sex, the lipoxygenase (LOX)-derived dihomo-gamma-linoleic acid metabolite, 15(s)-hydroxyeicosatrienoic acid (15(s)-HETrE; detectable in n¼81) was lower in SIVD (F 1,80 ¼11.51, p¼0.001) but not AD (F 1,80 ¼2.74, p¼0.102). The LOX derived arachidonic acid metabolite, 15-hydroxyeicosatetraenoic acid (15-HETE; detectable in n¼65), was lower in AD (F 1,64 ¼4.98, p¼0.032) but not SIVD (F 1,64 ¼0.05, p¼0.821). In participants with extensive SIVD but no AD (n¼28), two LOX derived linoleic acid metabolites, 9-hydroxyoctadecadienoic acid (9-HODE) and 13-HODE, were found to be positively associated with Z-scores on the Stroop (r¼0.523, p¼0.004 and r¼0.444, p¼0.018, respectively) and p¼0.001 and r¼0.557, p¼0.003, respectively), and negatively associated with periventricular WMH volume (r¼-0.386, p¼0.042; r¼-0.393, p¼0.039, respectively). Conclusions:The generation of LOX metabolites may be compromised differently in AD and SIVD. These metabolites might be protective against white matter injury and cognitive decline caused by subcortical ischemic vascular disease.

According to recent literature, there is a limited amount of data about the correlation of vitamin 25(OH)D, potassium (K), oxidative stress parameters, and other biomarkers with dyslipidemia, which is an established risk factor for cardiovascular diseases (CVDs). This study aims to investigate the correlation of lipid profile and atheromatic index TC/HDL with several biomarkers and oxidative stress parameters. A total of 102 volunteers, 67 with atheromatic index TC/HDL > 3.5 (Group A) and 35 with TC/HDL < 3.5 (Group B), aged from 26 to 78 years, participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low- and high-density lipoproteins (LDL and HDL), vitamin 25(OH)D [25(OH)D], potassium (K), sodium (Na), lactose dehydrogenase (LDH), liver enzymes including serum glutamic oxaloacetic and glutamic pyruvic transaminases (SGOT and SGPT), gamma-glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) were analyzed using standard photometric methods. Oxidative stress parameters such as reactive oxygen species (ROS) were detected with fluorometric methods, whereas total oxidative (TOS) and antioxidative status (TAS) were measured with spectrophotometric methods. According to the results, negative correlations of HDL (r = −0.593) and 25(OH)D (r = −0.340) and K (r = −0.220) were found, and positive expected correlations of LDL (r = 0.731), TC (r = 0.663), and TG (r = 0.584) with atheromatic index in the total studied sample were found. In conclusion, patients with a dyslipidemic profile should frequently check not only their lipid profile but also other biomarkers such as 25(OH)D, potassium, and oxidative stress markers to predict dyslipidemia and avoid subsequent disorders.