RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2'-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION.

Background: The 2'-O-methyltransferase is responsible for the capping of SARS-CoV-2 mRNA and consequently the evasion of the host's immune system. This study aims at identifying prospective natural inhibitors of the active site of SARS-CoV-2 2'O-methyltransferase (2'-OMT) through an in silico approach. Materials and methods: The target was docked against a library of natural compounds obtained from edible African plants using PyRx - virtual screening software. The antiviral agent, Dolutegravir which has a binding affinity score of -8.5 kcal mol-1 with the SARS-CoV-2 2'-OMT was used as a standard. Compounds were screened for bioavailability through the SWISSADME web server using their molecular descriptors. Screenings for pharmacokinetic properties and bioactivity were performed with PKCSM and Molinspiration web servers respectively. The PLIP and Fpocket webservers were used for the binding site analyses. The Galaxy webserver was used for simulating the time-resolved motions of the apo and holo forms of the target while the MDWeb web server was used for the analyses of the trajectory data. Results: The Root-Mean-Square-Deviation (RMSD) induced by Rhamnetin is 1.656A0 compared to Dolutegravir (1.579A0). The average B-factor induced by Rhamnetin is 113.75 while for Dolutegravir is 78.87; the Root-Mean-Square-Fluctuation (RMSF) for Rhamnetin is 0.75 and for Dolutegravir is 0.67. Also, at the active site, Rhamnetin also has a binding affinity score of -9.5 kcal mol-1 and forms 7 hydrogen bonds compared to Dolutegravir which has -8.5 kcal mol-1 and forms 4 hydrogen bonds respectively. Conclusion: Rhamnetin showed better inhibitory activity at the target's active site than Dolutegravir.

Emergency medicine: magnesium sulphate injections and their pharmaceutical quality concerns.

OBJECTIVES: World Health Organization has recognized magnesium sulphate as the drug of choice for prevention and treatment of fits associated with preeclampsia and eclampsia which are amongst the leading causes of maternal morbidity and mortality. In this study, the pharmaceutical quality of magnesium sulphate injections marketed in Anambra state was assessed. METHODS: Ninety samples of magnesium sulphate obtained from the 3 senatorial zones in Anambra state were subjected to identification tests, microbiological analysis consisting of Growth promotion test, sterility and endotoxin test. Content analysis using titrimetric method and pH analysis were also carried out on the samples. RESULTS: Twenty percent (20%) of samples obtained from Onitsha failed identification test as they had no Registration number in Nigeria. All samples subjected to the microbiology tests (sterility and endotoxin test) passed. Twenty percent (20%) and thirty-three percent (33.3%) of samples sourced from Onitsha and Nnewi respectively failed the pH analysis test. All the samples passed microbiological tests and had their Active Pharmaceutical Ingredients (API) within the acceptable limit. CONCLUSIONS: This study reveals that there are still some substandard magnesium sulphate injections in circulation in the locality. The supply chain of these drugs should be monitored to ensure a reduction in the incidences of substandard magnesium sulphate and positive therapeutic outcome which translates to reduced maternal mortality associated with pre-eclampsia and eclampsia in Nigeria.

The Pharmacobiochemical Effects of Ethanol Extract of Justicia secunda Vahl Leaves in Rattus Norvegicus.

PURPOSE: This study evaluated the biochemical effects of ethanol leaves extract on Wistar rats and also shed light on its constituents and phytonutrients. METHODS: The ethanolic extract of J. secunda leaves was prepared using conventional methods. Then, proximate and phytochemical analyses of the extracts were carried out using several methods previously reported in the literatures. The biochemical studies were also carried out as reported in previous literatures. RESULTS: The ethanolic leaves extract contains appreciable quantities of phytonutrients and micronutrients as well as phytochemical constituents. The LD50 of the extract was determined to be 3800mg/kg body weight. There was a dose-dependent elevation of the blood sugar in comparison with the control. There was no significant increase on the bilirubin and liver enzymes levels or on the haematological parameters of the lab animals. The extract significantly elevated the lipid profile (P value < 0.0001), the glomerular filtration rate (increased creatinine and blood urea levels - P value < 0.0001), the serum electrolytes and the animals' weight. There was a significant decrease in the anion gap (P value < 0.01). CONCLUSION: The ethanol leaf extract of Justicia secunda has negative cardiac and renal effects on Wistar rats, causing increased lipid profile values, creatinine and blood urea levels in the experimental animals compared with control. The LD50 is below the safety level. Caution should be exercised as the biochemical profiles of cardiac and renal effects do not seem to be promising and the LD50 is below the safety level.

Immunoinformatics and Vaccine Development: An Overview.

The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/re-emerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

Winning the War against Multi-Drug Resistant Diarrhoeagenic Bacteria.

Drug-resistant-diarrhoeagenic bacteria are currently emerging healthcare challenge. This study investigated the effects of Vernonia amygdalina, Garcinia kola, tetracycline and metronidazole combinations on such bacteria. Agar well diffusion method was employed to determine the inhibitory effects of the herbal extracts on diarrhoeagenic bacteria while Time-Kill Assay was used to determine bactericidal effects of the extracts against test isolates. Interactions between plant extracts and antibiotics were investigated using Checkerboard assay. Minimum inhibitory concentrations of the extracts against the bacterial isolates ranged between 3.125-50 mg/mL, while those of tetracycline and metronidazole ranged from 30-50 µg/mL. Synergism was observed against B. cereus and S. aureus for metronidazole + aqueous G. kola at all ratios. Generally, the combinations aqueous G. kola + ethanolic G. kola and aqueous G. kola + ethanolic V. amygdalina showed more pronounced synergism against the Staphylococcus aureus than B. cereus isolates with the fractional inhibition concentration (FIC) indices ranging from 0.32-0.95. Synergism of tetracycline + crude extracts and metronidazole combinations were more pronounced on the test isolates and especially on the Gram-negative organisms with FIC indices ranging from 0.41-0.91. Conclusion: The herbal extracts combinations and extracts-antibiotics combinations are synergistic on diarrhoeagenic bacteria at defined combination ratios.

Carbapenem-Resistant Enterobacteriaceae Posing a Dilemma in Effective Healthcare Delivery.

The emergence and spread of Carbapenem-resistant Enterobacteriaceae (CRE) is seriously posing threats in effective healthcare delivery. The aim of this study was to ascertain the emergence of CRE at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH) Awka. Biological samples were collected from 153 consenting patient from 5 clinics in the hospital. The isolates were identified using standard microbiological protocols. Susceptibility to meropenem was done using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. A total of 153 patients were recruited in this study. About one half of those from rural, 63.64% from Sub-urban and 42.27% from urban areas had significant E. coli and Klebsiella spp infections. The male: female ratio of the Enterobacteriaceae infection was 1:1. Almost as much inpatient as outpatient study participants had the infections. The infections were observed mostly on participants with lower educational status. The unmarried individuals were most infected compared to their married counterparts. Enterobacteriaceae infection rate was 50.98%. Of this, 28.21% had CRE infection while the overall prevalence of the CRE in the studied population was 14.38% (22/153). This study shows that CRE is quickly emerging in both community and hospital environments. Klebsiella spp was the most common CRE in this hospital especially Klebsiella oxytoca. Hospitalization was a strong risk factor in the CRE infections. Rapid and accurate detection is critical for their effective management and control.

The Bacteriology and Its Virulence Factors in Neonatal Infections: Threats to Child Survival Strategies.

BACKGROUND: Neonatal infection refers to the infection of the newborn during the first twenty-eight days of life. It is one of the causes of infant morbidity and mortality worldwide. The aim of the study is to determine the relative contribution of the different pathogens to the overall disease burden. It will also determine the mechanisms of virulence of these pathogens that cause neonatal infections at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH), Awka. METHODS: Biological samples were collected from 30 neonates admitted at the special care baby unit (SCBU) of COOUTH and cultured using selective media and nutrient agar. The isolates were identified using microbiological and biochemical tests. The antibiogram study was determined using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. Several methods previously reported in literature were used for the characterization of the virulence factors. RESULTS: From the 30 blood samples collected, Pseudomonas spp. (19.7%), Escherichia coli (23%), Salmonella spp. (24.6%), and Staphylococcus aureus (32.8%) were isolated. Male to female ratio of study population was 1.5: 1. The isolates were 100 % resistant to ticarcillin, cephalothin, ceftazidime, and cefuroxime but appreciably susceptible to only levofloxacin (88.85%). They were moderately susceptible to ceftriaxone/sulbactam (39.05%) and azithromycin (26.46%). Common virulence factors identified among the isolates (up to 90 %) were hemolysin, biofilm formation, and acid resistance. Less common virulence factors were proteases (50 %), deoxyribonucleases (50 %), enterotoxins (63%), and lipopolysaccharide (70%). The virulence factors were found mostly among the S. aureus isolates. CONCLUSIONS: Pseudomonas spp., Escherichia coli, Salmonella spp., and Staphylococcus aureus were implicated in neonatal infections in the center and most of them were resistant to conventional antibiotics. The organisms showed marked virulence and multidrug resistance properties. Levofloxacin, a fluoroquinolone, had superior activity on the isolates compared to other antibiotics used in the study.