Molecular Docking and ADMET Prediction of Natural Compounds towards SARS Spike Glycoprotein-Human Angiotensin-Converting Enzyme 2 and SARS-CoV-2 Main Protease.

More than a decade ago, a novel coronavirus that infects humans, bats, and certain other mammals termed severe acute respiratory syndrome coronavirus (SARS-CoV) caused an epidemic with ~ 10% case fatality, creating global panic and economic damage. Recently, another strain of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an infectious disease (COVID-19) in humans which was detected for the first time in Wuhan, China. Presently, there is no specific therapy available for the treatment of COVID-19. However, social distancing, patient isolation, and supportive medical care make up the current management for this current infectious disease pandemic. The present in silico study evaluated the binding affinities of some natural products (resveratrol, xylopic acid, ellagic acid, kaempferol, and quercetin) to human angiotensin-converting enzyme 2 and coronavirus (SARS-CoV-2) main protease compared to chloroquine, an inhibitor known to prevent cellular entry and replication of the coronavirus. The respective binding energies of the selected natural compounds and chloroquine towards the proteins were computed using PyRx virtual screening tool. The pharmacodynamic and pharmacokinetic attributes of the selected compounds were predicted using admetSAR. Molecular docking analysis showed that the natural compounds had better scores towards the selected protein compared to chloroquine with polar amino acid residues present at the binding sites. The predicted ADMET properties revealed the lower acute oral toxicity of the natural products compared to chloroquine. The study provides evidence suggesting that the relatively less toxic compounds from the natural sources could be repositioned as anti-viral agents to prevent the entry and replication of SARS-CoV-2.

Clinicopathological Pattern and Management of Primary Lung Cancer in Ilorin, Nigeria.

BACKGROUND: Lung cancer incidence and mortality rates have increased in some low and medium-resourced countries. OBJECTIVES: This study aimed to describe the clinicopathological pattern and management of lung cancer seen in our setting. METHODS: We reviewed cases of pulmonary neoplasm diagnosed and managed at the University of Ilorin teaching hospital over eight years. Cases with tissue diagnosis were enrolled in the study and relevant clinical data were collected from the medical record using a proforma. DESIGN: Hospital-based retrospective study. RESULTS: Out of the 71 cases of primary lung cancer reviewed, 44(62%) were males and the male to female ratio was 2:1. The mean age was 62±14 years and the occurrence was highest in aged 50-69 years. Thirty (42.3%) with histories of tobacco smoking were males. Adenocarcinoma accounted for 34(54.9%), 23(32.4%) were squamous cell carcinoma, 2(2.8%) were large cell carcinoma and 6(8.5%) were other histological variants. The majority (82.7%) presented at stage III-IV lung cancers, 56.3% had malignant pleural effusion and 74.6% received palliative care. Thirty-eight (53.3%) had chest tube drainage, 19(26.7%) underwent chemical pleurodesis and 22(31.0%) received Cisplatin-based systemic chemotherapy. One patient had curative surgery and none received radiotherapy. At 12 months, 4 (5.6%) were still alive, 14(19.7%) cases had medical records of their death and 53(74.7%) were lost to follow up. CONCLUSION: This study has highlighted the clinicopathological trend, high rate of mortality and late presentation of lung cancer in our setting. There is a need to increase the awareness of the warning signs and risk factors to ensure early detection and facilitate curative therapy.

CONTEXTE: L'incidence du cancer du poumon et les taux de mortalité ont augmenté dans certains pays à faibles et moyennes ressources. OBJECTIFS: Cette étude visait à décrire le modèle clinicopathologique et la prise en charge du cancer du poumon observé dans notre milieu. MÉTHODES: Nous avons passé en revue les cas de néoplasme pulmonaire diagnostiqués et pris en charge à l'hôpital universitaire de l'Université d'Ilorin pendant huit ans. Les cas avec diagnostic tissulaire ont été inclus dans l'étude et les données cliniques pertinentes ont été collectées à partir du dossier médical à l'aide d'un formulaire. CONCEPTION: étude rétrospective en milieu hospitalier. RÉSULTATS: Sur les 71 cas de cancer du poumon primitif examinés, 44 (62%) étaient des hommes et le ratio homme / femme était de 2:1. L'âge moyen était de 62 ± 14 ans et la fréquence était la plus élevée chez les 50 à 69 ans. Trente (42,3%) ayant des antécédents de tabagisme étaient des hommes. L'adénocarcinome représentait 34 (54,9%), 23 (32,4%) étaient des carcinomes épidermoïdes, 2 (2,8%) étaient des carcinomes à grandes cellules et 6 (8,5%) étaient d'autres variantes histologiques. La majorité (82,7%) des cancers du poumon de stade III-IV, 56,3% ont eu un épanchement pleural malin et 74,6% ont reçu des soins palliatifs. Trente-huit (53,3%) ont eu un drainage par sonde thoracique, 19 (26,7%) ont subi une pleurodèse chimique et 22 (31,0%) ont reçu une chimiothérapie systémique à base de cisplatine. Un patient a subi une chirurgie curative et aucun n'a reçu de radiothérapie. À 12 mois, 4 (5,6%) étaient encore en vie, 14 (19,7%) cas avaient un médical de leur décès et 53 (74,7%) étaient perdus de vue. CONCLUSION: Cette étude a mis en évidence la tendance clinicopathologique, le taux élevé de mortalité, et la présentation tardive du cancer du poumon dans notre milieu. Il est nécessaire d'accroître la sensibilisation aux signes avant-coureurs et aux facteurs de risque pour assurer une détection précoce et faciliter la thérapie curative. MOTS CLÉS: Clinico-pathologique, modèle, prise en charge, cancer du poumon, néoplasme, Nigéria.

In silico Design of a Vaccine Candidate for SAR S-CoV-2 Based on Multiple T-cell and B-cell Epitopes.

Coronaviruses (2019-nCoV) are large single-stranded RNA viruses that usually cause respiratory infections with a crude lethality ratio of 3.8% and high levels of transmissibility. There is yet no applicable clinical evaluation to assess the efficacy of various therapeutic agents that have been suggested as investigational drugs against the viruses despite their respective supposed hypothetical claims due to their antiviral potentials. Moreover, the development of a safe and effective vaccine has been suggested as an intervention to control the 2019-nCoV pandemic. However, a major concern in the development of a 2019-nCoV vaccine is the possibility of stimulating a corresponding immune response without enhancing the induction of the disease and associated side effects. The present investigation was carried out by predicting the antigenicity of the primary sequences of 2019-nCoV structural proteins and identification of B-cell and T-cell epitopes through the Bepipred and PEPVAC servers, respectively. The peptides of the vaccine construct include the selected epitopes based on the VaxiJen score with a threshold of 1.0 and ß-defensinas an adjuvant. The putative binding of the vaccine constructs to intracellular toll-like receptors (TLRs) was assessed through molecular docking analysis and molecular dynamics simulations. The selected epitopes for the final vaccine construct are DPNFKD, SPLSLN, and LELQDHNE as B-cell epitopes and EPKLGSLVV, NFKDQVILL, and SSRSSSRSR as T-cell epitopes. The molecular docking analysis showed the vaccine construct could have favorable interactions with TLRs as indicated by the negative values of the computed binding energies. The constructed immunogen based on the immune informatics study could be employed in the strategy to develop potential vaccine candidates against 2019-nCoV.

Outcomes of intensive care management of traumatic brain injury in a resource-challenged tertiary health centre.

BACKGROUND: Improved surgical care and protocol-driven intensive care interventions for head injured patients have contributed to the overall reduction in mortality in developed countries. The aim of this study is to highlight the clinical outcomes of patients with severe traumatic brain injury managed in the multispecialty ICU of our institution. STUDY DESIGN: The medical records of all patients with severe TBI managed in our 3-bedded non-dedicated ICU over a 24-month period were reviewed. Data on demographic characteristics, mechanism of injury, neuroimaging and interventions were obtained and the primary outcome measure was the mortality. RESULTS: Fifty one patients, age ranged from 2-75 years and median age of 30 years were studied. The male sex was more involved (M;F of 12;1) and motorcycle crashes caused the majority of the injury (19,{37%}). None of the patients received pre-hospital care and about half (25 {49 %}) presented six hours post trauma. Cranial CT scan showed intracranial haemorrhage in 7 of the 21 patients stabled for neuroimaging. Overall mortality was 70%, with highest mortality recorded in those who did not have post injury brain CT scan (58% vs 82%, p = 0.066). CONCLUSION: Mortality from severe TBI is very high in our environment where routine pre-hospital care and prompt transfer to neurosurgical centres are not practiced. Lack of facilities for monitoring intracranial pressure and arterial blood gases in our ICU also contributed to the high mortality.

Outcome of management of complicated extragonadal teratoma in a resource poor setting.

BACKGROUND: Extragonadal teratomas (EXGTs) are ubiquitous in the human body; hence, they have varied presentation. In underdeveloped areas presentation and management are affected by socio-economic, cultural and health facilities factors. The aim of this study was to review the outcome of management of complicated EXGT in a tertiary health centre. MATERIALS AND METHODS: A review data of paediatric patients with EXGT was done between January 1999 and December 2012. Variables reviewed were bio-data, mode of presentation and site of tumour, comorbidity, treatments and outcome. The data was analysed with Statistical Package for Social Sciences (SPSS (R)) version 16.0. RESULTS: There were 21 complicated EXGT (77.8%) among 27 children, age ranges from 4 days to 16 years (median = 2 years). Male:Female ratio of 1:2. The complications per region of the body at presentation were cervical 4 (66.7%), mediastinal 2 (100%), abdominal 3 (75%) and sacrococcygeal 12 (75%). The complications were respiratory distress 6, intestinal obstruction 5, faecal incontinence 2, bladder outlet obstruction 3, malignant transformation 5, ruptured sacrococcygeal teratoma 2, ulcerated tumour 2, anaemia 3 and malnutrition 3. There were 5 (23.8%) progressive disease post-excision outside our facility. Excision biopsy was successful in 19 (85%) patients two of which had neoadjuvant cytotoxic therapy. Overall mortality was 5 (23.8%) (septicaemia, anaemia, respiratory distress, renal failure) and post-excision mortality was 11.8% (endotracheal tube blockage and progressive disease). CONCLUSION: Delay presentation (due to local belief, ignorance and poverty) malnutrition, sepsis, malignant transformation characterised presentation of children in this study and the lack of paediatric intensive care unit facility and intensivists compromised survival of children with EXGT.

Intestinal obstruction: a rare complication of channeling transurethral resection of the prostate (TURP): a case report.

INTRODUCTION: Channeling transurethral resection of the prostate is a recognized form of adjunctive treatment in the treatment of patients with prostate cancer. Despite the fact that complications arising from the procedure have been on the decline, rare complications like intestinal obstruction may occur. CASE PRESENTATION: This is a case report of a 56 year old man who developed mechanical intestinal obstruction few days after a channeling TURP for advanced CaP. CONCLUSION: The report highlights the possibility of intestinal obstruction as a secondary event following a silent urinary bladder perforation during channeling TURP. Early recognition and intervention were responsible for the good outcome in this patient.

Gall bladder perforation: report of 3 cases.

We report 3 cases of gall bladder perforation treated in this centre between January 1996 and June 2001. These were compared with Neimier's original classification of types of gall bladder perforation and areas of difficulty in management emphasised. The literature was also reviewed.

Massive haematochezia after uterine evacuation: an uncommon cause of lower gastrointestinal bleeding.

We report a case of a 30-year-old Para 2 + 1 who presented with massive haematochezia 7 days after uterine evacuation for an incomplete abortion. Difficulty in pre-operative diagnosis in this type of presentation and treatment is highlighted and the literature reviewed.