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 Method: 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 as 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 as 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

Targeting specific checkpoints in the management of SARS-CoV-2 induced cytokine storm

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.https://www.mdpi.com/journal/lifeam2023Pharmacolog

Traditional consumption of the fruit pulp of Chrysophyllum albidum (Sapotaceae) in pregnancy may be serving as an intermittent preventive therapy against malaria infection

Background: The bark of Chrysophyllum albidum is reported to possess antimalarial property. The fruit pulp of C. albidum consumed by pregnant women of south eastern Nigeria may also possess antimalarial activity. The present preliminary study investigated the antimalarial potential of the pulp juice and seed of C. albidum. Methods: Schizonticidal activity was evaluated using the Peter's 4-day suppressive test. The prophylactic and curative antimalarial activities of the extracts were evaluated in Albino mice inoculated with Plasmodium berghei. Results: The oral acute toxic dose of the pulp extract is beyond 5000 mg/kg. The seed and pulp possess both suppressive and curative properties. The seed extract suppressed early infection by 72.97% and 97.30%, at 500 and 1000 mg/kg, respectively. The pulp juice recorded 72.97% and 81.08%, at 500 and 1000 mg/kg, respectively. At 500 mg/kg dose, the level of parasite control on Day 7 was the same (96.10%) for both seed and pulp. Conclusion: This study demonstrates the presence of antimalarial constituents in the chemically uncharacterized samples (fruit pulp and seed) of C. albidum. Its ethnomedicinal use may be valuable in pregnancy where it may possibly serve as an intermittent preventive therapy against malaria

Safety evaluation in mice of the childhood immunization vaccines from two south-eastern states of Nigeria

Objective:: To check the effects of the vaccines on the hematopoietic system and weight of mice after immunization. Methods:: The study was done with the Expanded Programme on Immunization vaccines donated by the Ministries of Health of Abia and Imo States of Nigeria. The vaccines were collected from the cold-chain stores and transported in vaccine carriers to the cold-chain facility in Nnamdi Azikiwe University Teaching Hospital within 3 hours of collection. They were used to immunize a total of 160 mice. The Ethics Committee of Nnamdi Azikiwe University Teaching Hospital, Nnewi of Anambra State, Nigeria approved the protocol. Results:: Mice body weight changes test showed that the mice all had increased body weight at Days 3 and 7 post-immunization and none died during the 7 d post-immunization observation. The percentage weight gains of the mice compared with the control were 69%, 70%, 64%, 63%, 65% and 68% for oral polio vaccine, diphtheria-pertussis-tetanus, bacillus Calmette–Guérin, measles, yellow fever and hepatitis B vaccines respectively collected from Imo State. The mice immunized with oral polio vaccine, pentavalent, bacillus Calmette–Guérin, measles, yellow fever and hepatitis B vaccines collected from Abia State had 123%, 114%, 121%, 116%, 142% and 119% weight gain respectively compared with the control. Leukocytosis promoting toxicity test showed that none of the vaccines was able to induce proliferation of leukocytes up to ten folds. Leukopenic toxicity test showed that all the vaccines had an leukopenic toxicity test value higher than 80% of the control (physiological saline). Conclusions:: The vaccine samples tested were safe and did not affect the hematopoietic system adversely. The storage conditions of the vaccines in the States’ cold-chain stores had not compromised the safety of the vaccines

Health professionals’ knowledge about relative prevalence of hospital-acquired infections in Delta State of Nigeria

Introduction: Hospital-acquired infections (HAIs) constitute a serious global public health challenge, causing great suffering to many people across the globe at any given time. This study ascertains the knowledge of health professionals on the challenge and their compliance with infection control measures. Methods: Validated questionnaires were administered to 660 health professionals and supported with face-to-face interview. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 16.0 (SPSS Inc, USA). Chi-square was used to test association between the independent and the outcome variables. Cut-off point for statistical significance was 5% (p value<0.05). Results: UTIs (61.4%) followed by Hospital-acquired Pneumonia (55.6%) were known to be the most prevalent HAIs in government hospitals while Staphylococcus aureus (54.4%) was reported the most microbial agent. In private health facilities, Hospital-acquired Pneumonia was known to be the most common (66.1%) while Pseudomonas aeruginosa was the most reported culprit. HAIs were reported to have occurred more in government hospitals and catheterization was the commonest modes of transmission in both health facilities. Conclusion: The prevalence of HAIs in this state was reported to be high. Although health-care professionals have good knowledge of HAIs, active effort is not always made to identify and resolve them. Standardized surveillance of HAIs is urgently needed.Pan African Medical Journal 2016; 2

The pandemic COVID-19: a tale of viremia, cellular oxidation and immune dysfunction

COVID-19, caused by SARS-CoV-2 is a tester of the immune system. While it spares the healthy, it brings severe morbidity and in a few cases, mortality to its victims. This article aims at critically reviewing the key virulence factors of COVID-19 which are the viremia, cellular oxidation and immune dysfunction. The averse economic effect of certain disease control measures such as national lock-downs and social distancing, though beneficial, makes them unsustainable. Worse still is the fact that wild animals and domestic pets are carriers of SARS-CoV-2 suggesting that the disease would take longer than expected to be eradicated globally. A better understanding of the pathological dynamics of COVID-19 would help the general populace to prepare for possible infection by the invisible enemy. While the world prospects for vaccines and therapeutic agents against the SARS-CoV-2, clinicians should also seek to modulate the immune system for optimum performance. Immunoprophylactic and immunomodulatory strategies are recommended for the different strata of stakeholders combating the pandemic with the hope that morbidities and mortalities associated with COVID-19 would be drastically reduced

Healthcare waste management in selected government and private hospitals in Southeast Nigeria

Objective: To assess healthcare workers' involvement in healthcare waste management in public and private hospitals. Methods: Validated questionnaires (n = 660) were administered to randomly selected healthcare workers from selected private hospitals between April and July 2013. Results: Among the healthcare workers that participated in the study, 187 (28.33%) were medical doctors, 44 (6.67%) were pharmacists, 77 (11.67%) were medical laboratory scientist, 35 (5.30%) were waste handlers and 317 (48.03%) were nurses. Generally, the number of workers that have heard about healthcare waste disposal system was above average 424 (69.5%). More health-workers in the government (81.5%) than in private (57.3%) hospitals were aware of healthcare waste disposal system and more in government hospitals attended training on it. The level of waste generated by the two hospitals differed significantly (P = 0.0086) with the generation level higher in government than private hospitals. The materials for healthcare waste disposal were significantly more available (P = 0.001) in government than private hospitals. There was no significant difference (P = 0.285) in syringes and needles disposal practices in the two hospitals and they were exposed to equal risks (P = 0.8510). Fifty-six (18.5%) and 140 (45.5%) of the study participants in private and government hospitals respectively were aware of the existence of healthcare waste management committee with 134 (44.4%) and 19 (6.2%) workers confirming that it did not exist in their institutions. The existence of the committee was very low in the private hospitals. Conclusions: The availability of material for waste segregation at point of generation, compliance of healthcare workers to healthcare waste management guidelines and the existence of infection control committee in both hospitals is generally low and unsatisfactory

In vitro and in vivo antiplasmodial assays of selected Nigerian commercial herbal formulations

Introduction: Malaria remains a life-threatening disease, mainly in tropical and sub-tropical countries of the world. The problem caused by the disease is further compounded by the emergence and spread of multidrug resistant Plasmodium falciparum. Coupled with the poor distribution of modern health facilities, there is resurgence in the use of herbal remedies to treat malaria. In this study, we evaluated the antiplasmodial activities of six commercially available herbal formulations using in vivo and in vitro methods to assess their claimed antimalarial properties. Methods: The antiplasmodial activities of the six herbal formulations were assessed using Chloroquine sensitive P. falciparum parasite strain 3D7 using the SYBR Green in vitro method and the in vivo curative test (established infection) in Plasmodium berghei infected Mus musculus. Results: The six herbal formulations had values of IC50 > 100 μg/mL on 3D7 strain of P. falciparum compared to controls which had IC50 values of 6.92nM (Chloroquine) and 0.75nM (Artesunate). In the curative evaluation (in vivo) the herbal formulations significantly reduced parasitaemia on day 4 (26.3%-77.3 %) and day 7 (45.54%-94.81%) post-treatments (P < 0.05) when compared to the untreated group, which recorded high mortality rate. Conclusion: Findings made in this study lend support to the claim that these herbal formulations have antiplasmodial activities. Percentage inhibitions of parasitaemia of the formulations were all above 50% except M&T capsule which had lower percentage inhibition of parasitaemia

The Burden of Likely Rubella Infection among Healthy Pregnant Women in Abakaliki, Ebonyi State, Nigeria

The first 140 days of pregnancy are critical as regards rubella virus infection because of the likelihood of a poor pregnancy outcome. This study was undertaken to investigate the likelihood of exposure to poor pregnancy outcomes due to seroprevalence of rubella among selected pregnant women attending Mile Four Hospital, Abakaliki, Ebonyi State, Nigeria. The seroprevalence of rubella immunoglobulin M (IgM) antibodies was investigated among pregnant women. A total of 187 sera samples collected from the women were screened for rubella virus IgM antibody using the enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed using SPSS. The chi square test was performed at a P value of 0.05 significance and at a 95% confidence interval. Of the 187 pregnant women, 35 (18.72%) were positive for the rubella virus. Pregnant women within 26–30 years of age had the highest prevalence (26.15%), while those aged 35–40 years had the least prevalence. Married women had the highest prevalence (20.0%), followed by singles (16.67%) and widows (15.38%), while divorced pregnant women recorded the least prevalence (9.20%). Pregnant women with no formal education were more predisposed to rubella virus (22.22%) infection compared to their educated counterparts. Occupationally, full-time housewives had the highest prevalence (24.26%). The infection rates seemed to wane as pregnancy advanced. The first trimester had the highest prevalence (21.88%), followed by the second trimester (18.84%) and the third trimester (17.44%). Pregnant women living in urban areas had higher IgM seroprevalence (20.18%) than those in rural areas (16.67%). Furthermore, grand multigravidas were more infected (22.73%) than primigravidas (14.52%) and multigravidas (20.39%). The seroprevalence of rubella in this study was high, and it calls for general surveillance and mass immunization of children and females of childbearing age in the area to help reduce the incidence of congenital rubella syndrome

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