In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease

Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.     

Trypanosoma evansi kDNA minicircle found in the Venezuelan nectar-feeding bat Leptonycteris curasoae (Glossophaginae), supports the hypothesis of multiple origins of that parasite in South America

Trypanosoma evansi is a mammal generalist protozoon which causes negative effects on health and productivity in bovine and equine herds in South America, Europe, Asia and Africa. By molecular methods, we screened the presence of that parasite together with other trypanosome species in 105 bats of 10 species collected in arid zones of northern Venezuela. The first molecular approach was fluorescent fragment length barcoding (FFLB), which relies on amplification of relative small regions of rRNA genes (four loci) and fluorescence detection. By FFLB, 17 samples showed patterns of possible trypanosomatid infections. These samples were used to test presence of trypanosomes by PCR using the following DNA markers: V7–V8 SSU rRNA, gGAPDH and kDNA minicircle regions. Only in one individual of the nectar-feeding bat, Leptonycteris curasoae, we were able to amplify 1000 bp of the trypanosome kDNA minicircle. That PCR product was sequenced and the parasite species was determined by NCBI-BLAST and phylogenetic analysis. Both analyses showed that the minicircle sequence corresponds to Trypanosoma evansi. The phylogenetic analysis of the sequence obtained in this study clustered with a T. evansi sequence obtained in a Venezuelan capybara, Hydrochoerus hydrochaeris, and distant of others two T. evansi sequences obtained in a Colombian capybara and horse. This result supports the hypothesis of multiple origins of T. evansi in South America.     

Maternal Conditions and Perinatal Characteristics Associated with Autism Spectrum Disorder and Intellectual Disability

Background

As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions.

Aims

To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children.

Methods

The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes.

Results

In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk.

Conclusion

Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions.     

Characterization of polyclonal antibodies against ovine adipocyte plasma membranes.

1. Antisera against ovine adipocyte plasma membranes were developed in a mare. 2. These antisera showed a high degree of specificity to adipocyte plasma membranes and cross-reacted with other tissues. 3. Antisera cross-reactivity can be removed by adsorption of the antiserum with various tissue plasma membranes without significant reduction in their reactivity to adipocyte plasma membranes. 4. Antisera reacted with different affinity to adipocyte plasma membranes from different sites and from different species of animals.     

Genotypic Differences of Candida albicans and C. dubliniensis Isolates Related to Ethnic/Racial Differences within the Same Geographic Area

Candida albicans and C. dubliniensis genotype differences among Israeli ethnic groups were assessed. Isolates from Jews (51), Arabs (35) and Druze (25) were genotyped. The distributions among ethnic groups were not different, however they differed (p = 0.002) from global populations. Therefore, C. albicans and C. dubliniensis genotype distribution differences in Israel are related to changes in all ethnic groups.