Heterologous prime–boost doses of COVID-19 vaccines (‘mix-and-match’ approach) are being studied to test for the effectiveness of Oxford (AZD1222), Pfizer (BNT162b2), Moderna (mRNA-1273) and Novavax (NVX-CoV2373) vaccines for COVID in ‘Com-Cov2 trial’ in UK, and that of Oxford and Pfizer vaccines in ‘CombivacS trial’ in Spain. Later, other heterologous combinations of CoronaVac (DB15806), Janssen (JNJ-78436735), CanSino (AD5-nCOV) and other were also being trialled to explore their effectiveness. Previously, such a strategy was deployed for HIV, Ebola virus, malaria, tuberculosis, influenza and hepatitis B to develop the artificial acquired active immunity. The present review explores the science behind such an approach for candidate COVID-19 vaccines developed using 11 different platforms approved by the World Health Organization. The candidate vaccines’ pharmaceutical parameters (e.g. platforms, number needed to vaccinate and intervals, adjuvanted status, excipients and preservatives added, efficacy and effectiveness, vaccine adverse events, and boosters), and clinical aspects must be analysed for the mix-and-match approach. Results prime–boost trials showed safety, effectiveness, higher systemic reactogenicity, well tolerability with improved immunogenicity, and flexibility profiles for future vaccinations, especially during acute and global shortages, compared to the homologous counterparts. Still, large controlled trials are warranted to address challenging variants of concerns including Omicron and other, and to generalize the effectiveness of the approach in regular as well as emergency use during vaccine scarcity.

Serine/threonine kinase 16 (STK 16) is involved in many facets of cellular regulation; activation of STK 16 plays a crucial role in the migration of cancer cells. Therefore, it is a novel target for the discovery of anticancer agents. Herein, virtual screening and dynamics simulation were used to screen a large library of natural compounds against STK 16 using Schrodinger suit 2021-2 and GROMACS 2021.6. The results predicted five molecules with high binding affinity against the target, with NPC132329 (Arcyriaflavin C) and NPC160898 having higher binding affinity and molecular mechanics generalized born surface area (MM/GBSA), suggesting that it is better than the standard inhibitor. The molecular dymanics (MD) simulation studies showed that the STK 16-NPC132329 complex has the lowest root mean square deviation, and STK 16-NPC160898 was the most stable compared with the standard drug and selective STK 16 inhibitor. The minimal fluctuation was observed in the STK 16-NPC132329 and STK 16-NPC160898 complexes based on the root mean square fluctuation trajectory with NPC132329 and NPC160898 forming 2 and 3 hydrogen bonds respectively with the amino acid residue of the target’s binding site. Overall, NPC132329 and NPC160898 are better STK 16 inhibitors than the standard drug and selective inhibitor, which can be further studied to discover novel anticancer drugs.

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

Focal adhesion (FA) play a critical role in many biological processes which include cell survival and cell migration. They serve as cellular anchor, allowing cells to stay attached to the extracellular matrix (ECM), and can also regulate cellular transduction. Previously, it has been suggested that vesicles such as endosomes could interact directly with FA or be implicated in their turnover. In this study, we investigated whether there is a relationship between FA and the early endocytic machinery in MDA-MB-231 cells. In this study, cell culture, transfection, time laps confocal microscopies, immunocytochemistry, western blotting, Cell fractionation and immunoprecipitation techniques were performed. Cells acutely treated with Dynasore, an inhibitor of dynamin, or with Pitstop 2, an inhibitor of clathryn-dependent endocytosis showed a reduction in the expression of early endosome biomarkers such as Rab5 and EEA1. Additionally, cells treated with these endocytic inhibitors exhibited an increase number and size of FA, as well as an increase FA turnover duration. This data was consistent with the reduction of the speed of cell migration. We demonstrated that Rab5- and EEA1-positive early endosomes were found to be colocalized with internalized FA. The present study suggests that there is a link between FA and early endosome markers, which indicates that the early endosomes may be involved in FA dynamics.

The ABO blood type has been reported to be associated with several diseases such as hepatitis and malaria. Recently, some studies have reported that people with O blood type are protected against COVID-19, while people with A blood type are more susceptible to contract this disease. Here, we analysed data from 5668 COVID-19 patients along with the same number of control samples in a study population in Iraq. Our analysis confirms that people with O blood type are protected partially against COVID-19. Notably, we demonstrate that people with RhD- are more susceptible to contract COVID-19 than people with RhD+ blood type. The blood types are associated with some clinical symptoms such as headache and asthenia of COVID-19, but there is no association with other symptoms. There is no association between blood types and deaths among COVID-19 patients. This study suggests that in addition to ABO, RhD blood type influences the susceptibility to contract COVID-19. Overall, we conclude that susceptibility/protection against COVID-19 may not be determined based only on blood types among the global population as this might vary based on a number of other factors such as ethnicity, geographical locations, occupation and the level of exposure to infected people.

Antimicrobial resistance (AMR) generates serious negative impacts on health-care systems worldwide, and Iraq is not an exception. To uncover the prevalence of AMR and to visualize the magnitude of the multidrug-resistant (MDR) dilemma in Iraqi hospitals, this study is carried out. A total of 11592 clinical records from ten different health-care facilities in seven Iraqi provinces are collected and analyzed. Our data show that 4984 (43.0%) of all clinical samples are negative for bacterial growth. In adults, Gram-negative bacteria (GNB) represented 48.9% and Gram-positive bacteria (GPB) represented 51.1% of clinical isolates; in children, GNB represented 60.8% and GPB represented 39.2%. Furthermore, in adults, Klebsiella pneumoniae (30.1%) and Staphylococcus aureus (40.8%) are among the most common GNB and GPB isolates, respectively. In children, K. pneumoniae (37.9%) and Staphylococcus haemolyticus (41.8%) are the most common GNB and GPB, respectively. Adults’ samples showed that Escherichia coli and Proteus mirabilis were the most resistant GNB; S. aureus and Staphylococcus epidermidis are among the most resistant GPB. In children, K. pneumoniae is found to be the most resistant GNB. This study confirms the persistence of antimicrobial resistance and multidrug-resistant gram-negative and gram-positive bacteria in adults and children alike. Ampicillin and oxacillin have been recognized as ineffective drugs in adults, and ampicillin, nafcillin, cefoxitin, and benzylpenicillin have been found to be highly resisted by pathogenic bacteria in children. The outcomes confirm the necessity of conducting AMR surveillance on a regular basis and establishing national antibiotic prescription guidelines to manage AMR development in Iraq.