Computational docking and scoring techniques have revolutionized structural bioinformatics by providing unprecedented insights on key aspects of ligand-receptor interaction. Docking is used for optimizing known drugs and for identifying novel binders by predicting their binding mode and affinity. AutoDock and AutoDockTools are free of charge techniques that have been extensively cited in the literature as essential tools in structure-based drug design. Moreover, these methods are fast enough to permit virtual screening of ligand libraries containing tens of thousands of compounds. However using Autodock requires some knowledge in programming which creates a limitation for biologists and makes them prone for commercial applications. Here, we selected a relevant target involved in the progression of Alzheimer disease and provided a fully reproducible docking protocol. This example will show how docking techniques would be an important asset to identify new BACE1 inhibitors. The following friendly user tutorial targets both undergraduate and graduate students, allowing them to understand docking as a computational tool for structure-based drug design.

ObjectiveTo determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DesignLiving systematic review and meta-analysis. Data sOurcesMedline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists. stuDy selectiOnCohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. Data extractiOnAt least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. results 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I 2 =74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I 2 =0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I 2 =0%) and invasive ventilation (1.88, 1.36 to 2.60; I 2 =0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I 2 =9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I 2 =0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I 2 =0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I 2 =12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I 2 =0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I 2 =0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I 2 =55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I 2 =1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I 2 =not estimable; 1 st...

A sudden outbreak of pneumonia caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world facilitating the declaration of the resultant disease as a pandemic on March 2020. Predisposing factors for acquiring COVID-19 and for developing a severe form of this disease were postulated to be related to the epidemiological, clinical, and genetic characteristics of the patients. Biological markers such as the ABO blood group system were amongst these factors that were proposed to be linked to the variability in the disease course and/or the prevalence of the infection among different groups. Herein, we conducted the first retrospective case-control study from the Middle East and North Africa that tackles the association between the blood group types and the susceptibility to, as well as the severity of, SARS-CoV-2 infection. Contrary to the most acknowledged hypothesis, our results challenged the significance of this association and questioned the role of the ABO blood group system in dictating the severity of this disease. For future similar studies, we endorsed analyzing larger cohorts among different populations and we encouraged implementing more rigorous approaches to diminish the potential confounding effect of some underlying comorbidities and genetic variants that are known to be associated with the ABO blood group system.

Congenital heart disease is the leading cause of death in the first year of life. Mutations only in few genes have been linked to some cases of CHD. Thalidomide was used by pregnant women for morning sickness but was removed from the market because it caused severe malformations including CHDs. We used both in silico docking software, and in vitro molecular and biochemical methods to document a novel interaction involving Thalidomide, TBX5, and HAND2. Thalidomide binds readily to TBX5 through amino acids R81, R82, and K226 all implicated in DNA binding. It reduces TBX5 binding to DNA by 40%, and suppresses TBX5 mediated activation of the NPPA and VEGF promoters by 70%. We documented a novel interaction between TBX5 and HAND2, and showed that a p.G202V HAND2 variant associated with CHD and coronary artery diseases found in a large Lebanese family with high consanguinity, drastically inhibited this interaction by 90%. Similarly, thalidomide inhibited the TBX5/HAND2 physical interaction, and the in silico docking revealed that the same amino acids involved in the interaction of TBX5 with DNA are also involved in its binding to HAND2. Our results establish a HAND2/TBX5 pathway implicated in heart development and diseases.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threatening health issue. The progression of this viral infection occurs in the airways of the lungs with an exaggerated inflammatory response referred to as the "cytokine storm" that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications of COVID-19 and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs is Thalidomide; a historically emblematic controversial molecule that harbors an FDA approval for treating erythema nodosum leprosum (ENL) and multiple myeloma (MM). Based on just one-case report that presented positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Yet, the absence of substantial evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases, might cause a significant obstacle for carrying out further clinical evaluations. Herein, we will discuss the theoretical effectiveness of Thalidomide in attenuating inflammatory complications that are encountered in COVID-19 patients while pinpointing the lack of the needed evidences to move forward with this drug.