A labour of love : 'no schools for medical editors'

The editorial ‘No schools for medical editors’ struck a personal chord. The lot of the journal editor can indeed be lonely. The challenge of dealing with the manuscripts of colleagues, friends and associates is often fraught with difficulty, especially if one is based at an academic institution where many potential contributors are likely to reside. The editor's job remains a labour of love.www.samj.org.zaam201

A labour of love: 'No schools for medical editors'

The editorial ‘No schools for medical editors’ struck a personal chord. The lot of the journal editor can indeed be lonely. The challenge of dealing with the manuscripts of colleagues, friends and associates is often fraught with difficulty, especially if one is based at an academic institution where many potential contributors are likely to reside. The editor's job remains a labour of love.www.samj.org.zaam201

Gene of the month : the 2019-nCoV/ SARS-CoV- 2 novel coronavirus spike protein

The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called Covid-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV- 2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be ’preactivated’ and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV- 2 spike protein S.http://jcp.bmj.comam2020Chemical Patholog

Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies

Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease which is a collection of symptoms and infections caused by a retrovirus, human immunodeficiency virus (HIV). There is currently no curative treatment and therapy is reliant on the use of existing anti-retroviral drugs. Pharmacoinformatics approaches have already proven their pivotal role in the pharmaceutical industry for lead identification and optimization. In the current study, we analysed the binding preferences and inhibitory activity of HIV-integrase inhibitors using pharmacoinformatics. A set of 30 compounds were selected as the training set of a total 540 molecules for pharmacophore model generation. The final model was validated by statistical parameters and further used for virtual screening. The best mapped model (R = 0.940, rmsd = 2.847, Q2 = 0.912, se = 0.498, R2 pred = 0.847 and r2 m (test) = 0.636) explained that two hydrogen bond acceptor and one aromatic ring features were crucial for the inhibition of HIV-integrase. From virtual screening, initial hits were sorted using a number of parameters and finally two compounds were proposed as promising HIV-integrase inhibitors. Drug-likeness properties of the final screened compounds were compared to FDA approved HIV-integrase inhibitors. HIV-integrase structure in complex with the most active and final screened compounds were subjected to 50ns molecular dynamics (MD) simulation studies to check comparative stability of the complexes. The study suggested that the screened compounds might be promising HIV-integrase inhibitors. The new chemical entities obtained from the NCI database will be subjected to experimental studies to confirm potential inhibition of HIV integrase.University of Pretoria Vice Chancellor’s post-doctoral fellowship and National Research Foundation (NRF), South Africa.http://www.rsc.orgmolecularbiosystems2017-01-31hb2016Chemical Patholog

Continuing danger of glucose point-of-care test devices in the neonatal setting

No abstract available..http://www.samj.org.zaam2014ay201

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies

In the current study, we searched for potential DNA GyrB inhibitors using pharmacophorebased virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors were collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptor and hydrophobicity were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore it can be concluded that the compounds identified may have potential for the treatment of TB.National Research Foundation (NRF), South Africa.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1747-02852018-08-30hb2017Chemical Patholog

Simplified molecular input line entry system-based descriptors in QSAR modeling for HIV-protease inhibitors

Simplified molecular input line entry system (SMILES) descriptor based quantitative structure–activity relationship (QSAR) study was performed on a set of HIV-protease inhibitors to explore the structural functionalities for inhibition of the HIV-protease. For this purpose a set of HIV-inhibitors was collected from the literature along with their inhibitory constants. Monte Carlo optimization-based CORAL software was used for QSAR model development. Firstly, the dataset was divided into three random splits and secondly each split was divided into training, calibration, test and validation sets. A training set was used for model development whereas the rest of the sets were used to assess the quality of the developed models. QSAR models were developed with and without considering the influence of cyclic rings toward the inhibitory activity. Statistical quality of QSAR models developed from all splits was very good and fulfilled the criteria. The values of R2, Q2, s, R2 pred and r2 m explained that selected models are robust in nature and efficient enough to predict the inhibitory activity of the molecules outside of the training set. Statistical parameters also suggested that the presence of cyclic rings have a crucial impact on inhibitory activity. The molecular fragmentswere found to be important for the increase or decrease of the inhibitory activity which explained that models have mechanistic interpretation. This ligandbased QSAR study can provide clear directions to design and modulate potential HIV-protease inhibitors.The University of Pretoria Vice Chancellor's post-doctoral fellowship and the National Research Foundation (NRF), South Africa Innovation post-doctoral fellowship schemes.http://www.elsevier.com/locate/chemolab2017-04-30hb2016Chemical Patholog

Exploration of the structural requirements of HIV-protease inhibitors using pharmacophore, virtual screening and molecular docking approaches for lead identification

Please abstract in the article.The University of Pretoria Vice Chancellor's post-doctoral fellowship scheme.http://www.elsevier.com/locate/JMGMhj201