Molecular Detection of Hepatitis B Virus Among HBsAg Non-Reactive Blood of Donors

Despite all blood donations being tested routinely for HBsAg as a clinical marker of transmissible HBV, cases of post-transfusion hepatitis B virus infection are still being reported because molecular studies using Polymerase Chain Reaction (PCR) are not routinely available for Transfusion Transmissible Infection (TTIs) testing. In this study, we sought to use the PCR technique to re-screen donated blood that had already been proven to be HBsAg non-reactive with rapid diagnostic testing and ELISA. One hundred and eighty-five samples were obtained from a proportion of the blood deposited at the blood bank of the Federal Medical Center, Birnin-Kebbi, Nigeria. Socio-demographic parameters such as age group, status, ethnicity, occupation, and group PCV were obtained from donors' records. Nested PCR was employed to detect HBV DNA. Furthermore, genotyping was performed to determine HBV genotypes in the positive samples using PCR with genotype-specific primers. Of the 185 donors, it was observed that five (2.7%) of the population were positive for HBV. HBV is more common among people aged 18–30, singles, Hausa, and self-employed. In addition, the five positive samples were of genotype E. This study suggests the need to complement antibody-based tests with DNA testing for effective HBV screening and consequent safe transfusion. Keywords: Hepatitis B Virus; HBsAg; PCR; DNA testin

Inhibitors of α-glucosidase and Angiotensin-converting Enzyme in the Treatment of Type 2 Diabetes and its Complications: A Review on in Silico Approach

Background: The use of pharmacological agents to synergistically target key enzymes associated with carbohydrate digestion (α-glucosidase) and the hypertension-related angiotensin-converting enzyme (ACE) are critical strategies for the management of type 2 diabetes (T2D) and its end-stage complications. Furthermore, aside from their blood pressure-lowering effect, ACE inhibitors (ACEIs) are important therapeutic agents for preventing diabetic complications, highlighting their synergistic renoprotective and antihypertensive effects in diabetic patients who are normotensive and hypertensive. Objectives: We reviewed the safety and potent activity of phytochemicals discovered based on molecular docking and dynamics in recent years that could be used to treat T2D. Methods: We surveyed recently in silico drug discovery findings on α-glucosidase and ACE retrieved from the PubMed database. Computational in silico ADMET meta-analysis was performed on 57 compounds that could potentially inhibit α-glucosidase or ACE. Results: The review highlighted the fact that most hit compounds of α-glucosidase and ACE involving the use of molecular docking and molecular dynamics techniques are competitive and peptide inhibitors, respectively. Moreover, we found that most authors do not consider absorption distribution metabolism excretion toxicity (ADMET) studies on drug candidates, which is important in determining the safety profile of potent leads. Hence, we performed in silico ADMET meta-analysis of the reported compounds and found some inhibitors with an excellent pharmacological profile. Conclusion: We propose that further studies be conducted on these promising leads to demonstrate their efficacy and safety in the treatment of T2D

The discovery of some promising putative binders of KRAS G12D receptor using computer-aided drug discovery approach

A prospective target for the therapy of solid tumors is KRAS G12D, the most prevalent oncogenic KRAS mutation. However, despite decades of research that focused on the identification of druggable compounds against this highly challenging therapeutic cancer target, no drug has been clinically approved for the treatment of KRAS G12D-driven cancers. Herein, we employed computational techniques such as molecular docking and molecular dynamics simulations to investigate small-molecule compounds with the potential to bind putatively with KRAS G12D. The docking screening portrayed three compounds (Quercetin, Psoralidin, and Resveratrol) as promising drug candidates for the receptor target due to their higher binding affinities when compared with a known noncovalent, potent, and selective KRAS G12D inhibitor (MRTX1133). The stability analysis after 100000 ps molecular dynamics simulation suggests Quercetin as a more stable compound when compared with the other simulated chemical entities, including the referenced inhibitor (MRTX1133). In spite of our research findings, it will be too early to conclude the drug candidates can be advanced to the clinic for use with KRAS G12D cancer patients without extensive preclinical and clinical studies