Exploring the Traditional Chinese Medicine (TCM) database chemical space to target I7L protease from monkeypox virus using molecular screening and simulation approaches.

In the current study, we used molecular screening and simulation approaches to target I7L protease from monkeypox virus (mpox) from the Traditional Chinese Medicines (TCM) database. Using molecular screening, only four hits TCM27763, TCM33057, TCM34450 and TCM31564 demonstrated better pharmacological potential than TTP6171 (control). Binding of these molecules targeted Trp168, Asn171, Arg196, Cys237, Ser240, Trp242, Glu325, Ser326, and Cys328 residues and may affect the function of I7L protease in in vitro assay. Moreover, molecular simulation revealed stable dynamics, tighter structural packing and less flexible behaviour for all the complexes. We further reported that the average hydrogen bonds in TCM27763, TCM33057, TCM34450 and TCM31564I7L complexes remained higher than the control drug. Finally, the BF energy results revealed -62.60 ± 0.65 for the controlI7L complex, for the TCM27763I7L complex -71.92 ± 0.70 kcal/mol, for the TCM33057I7L complex the BF energy was -70.94 ± 0.70 kcal/mol, for the TCM34450I7L the BF energy was -69.94 ± 0.85 kcal/mol while for the TCM31564I7L complex the BF energy was calculated to be -69.16 ± 0.80 kcal/mol. Although, we used stateoftheart computational methods, these are theoretical insights that need further experimental validation.

SARS-CoV-2 associated pathogenesis, immune dysfunction and involvement of host factors: a comprehensive review.

Infectious diseases, especially viral infections, have emerged as a major concern for public health in recent years. Recently emerged COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been declared a pandemic by World Health Organization since March 2020. It was first identified in Wuhan, China, in December 2019 and has since claimed more than a million lives. Complicated symptoms are associated with rising incidence and fatality rates, while many of the vaccine candidates are in the final stages of clinical trials. This review encompasses a summary of existing literature on COVID-19, including the basics of the disease such as the causative agent's genome characterization, modes of transmission of the virus, pathogenesis, and clinical presentations like associated immune responses, neurological manifestations, the variety of host genetic factors influencing the disease and the vulnerability of different groups being affected by COVID-19.

Role of polymeric materials in preventing COVID-19 infection.

The safety of personal protective equipment (PPE) is very important, and so is the choice of materials used. The ability of electrostatic charges (ESCs) generated from the friction of engineered materials to attract or repel viruses has a significant impact on their applications. This study examined the ESCs generated on the surface of PPE used by healthcare workers to enhance their potential effectiveness in protecting the wearer from viruses. This is a crucial consideration for the newly emerged severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which has a negative charge. The magnitudes and signs of generated ESCs on the surfaces of the PPE were determined experimentally using an Ultra Stable Surface DC Voltmeter. The high negative ESCs acquired by the polyethylene disposable cap and facemask are expected to repel negatively charged viruses and prevent them from adhering to the outer layer of the material. Also, the choice of polypropylene for facemasks and gowns is excellent because it is an aggressively negatively charged material in the triboelectric series. This property guarantees that facemasks and gowns can repel viruses from the wearer. However, the positive ESCs generated on latex glove surfaces are of great concern because they can attract negatively charged viruses and create a source of infection. In conclusion, it is necessary to ensure that PPE be made of materials whose surfaces develop a negative ESC to repel viruses, as well as to select polyethylene gloves.

Mapping the effect of drugs on ACE2 as a novel target site for COVID-19 therapy.

Angiotensin converting enzyme 2 (ACE2) has potentially conflicting roles in health and disease. COVID-19 coronavirus binds to human cells via ACE2 receptor, which is expressed on almost all body organs. Boosting the ACE2 receptor levels on heart and lung cells may provide more cellular enter to virus thereby worsening the infection. Therefore, among the drug targets, ACE2 is suggested as a vital target of COVID-19 therapy. This hypothesis is based on the protective role of the drugs acting on ACE2. Therefore, this review discusses the impact and challenges of using ACE2 as a target in the current therapy of COVID-19.

The interplay between vitamin D and COVID-19: protective or bystander?

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Prediction of promiscuous epitopes in NSP2 of Chikungunya virus: An in-silico approach.

This study is focused towards developing a global consensus sequence of nonstructural protein 2 (NSP2), a protease of Chikungunya Virus (CHIKV) and predict immunogenic promiscuous T-cell epitopes based on various bioinformatics tools. To date, no epitope data is available for the Chikungunya virus in the IEDB database. In this study, 100 available nucleotide sequences of NSP2-CHIKV belonging to different strains were downloaded from the National Centre for Biotechnology Information (NCBI) database. The nucleotide sequences were subjected to translated sequencing using the EXPASY tool followed by protein alignment using the CLC workbench and a global consensus sequence for the respective protein was developed. IEDB tool was used to predict HLA-I and HLA-II binding promiscuous epitopes from the consensus sequence of NSP2-CHIKV. Thirty-four B-cell based epitopes are predicted and the promiscuous epitope is VVDTTGSTKPDPGD at position 341-354. Twenty-six MHC-I short peptide epitopes are predicted to bind with HLA-A. The promiscuous epitopes predicted to bind with HLA-A*01:01 are VTAIVSSLHY, SLSESATMVY, FSKPLVYY, QPTDHVVGEY at positions 317-326, 84-93, 535-544 and 15-24 with percentile ranks 0.17, 0.39, 0.51 and 0.81, respectively. Twenty-four MHC-II short peptide epitopes are predicted for HLA-DRB. The promiscuous epitope predicted to bind with HLA-DRB*01:01 is VVGEYLVLSPQTVLRS from 20-35 with a lowest percentile rank of 0.01. These predicted epitopes can be effective targets towards development of vaccine against CHIKV. Epitopes predicted in this study displayed good binding affinity, antigenicity and promiscuity for the HLA classes. These predicted epitopes can prove to be translationally important towards the development of CHIKV.

Infection control in hospitals managing drug-resistant tuberculosis in Pakistan: how are we doing?

Setting: Ten hospitals managing drug-resistant tuberculosis (TB) in Pakistan. Objective: To assess the implementation of TB infection control (IC) practices and reasons for non-adherence to guidelines. Design: This was a descriptive study conducted between April and October 2016 with three components: 1) non-participant observation of service delivery areas (SDAs) (n = 82) in hospitals (n = 10) using structured checklists; 2) exit interviews with 100 patients (10 per hospital); and 3) interviews with 100 health-care workers (HCWs, 10/hospital). Results: Of the 82 SDAs, posters were displayed in 34 (41%), mechanical ventilation was implemented in 79% and functional ultraviolet germicidal irradiation (UVGI) was available in only 26%. Patient interviews showed 50-65% adherence to triage and use of personal protective measures. Key reasons for non-adherence were lack of adequate supplies, discomfort using N-95 masks, a lack of knowledge or training, perceived non-cooperation by patients, poor maintenance of mechanical ventilators and UVGI due to unstable electricity supply, a lack of clarity in roles (no-one designated in charge) and staff shortages and subsequent workloads. Adherence to natural ventilation usage was poor for reasons related to climate and privacy. Conclusion: Implementation of TBIC measures in hospitals was suboptimal. Urgent measures need to be put in place, including retraining of HCWs, addressing weaknesses in mask and poster supplies and constant supervision and monitoring.

Contexte : Dix hôpitaux prenant en charge la tuberculose (TB) pharmacorésistante au Pakistan.Objectif : Evaluer la mise en œuvre des pratiques de lutte contre l'infection TB (CITB) et les raisons de la non-adhésion aux directives.Schéma : Étude descriptive réalisée entre avril et octobre 2016 avec trois composants : 1) observation non participative des zones de prestations de service (SDA) (n = 82) dans des hôpitaux (n = 10) grâce à des checklists structurées ; 2) entretiens de sortie avec 100 patients (10 par hôpital) ; 3) entretiens avec 100 prestataires de soins de santé (HCW, 10 par hôpital).Résultats : Parmi 82 SDA, des affiches ont été déployées dans 34 (41%) d'entre elles, une ventilation mécanique a été mise en œuvre dans 79% et un système fonctionnel d'irradiation par ultraviolets germicides (UVGI) a été disponible dans seulement 26%. Les entretiens avec les patients ont mis en évidence 50­65% d'adhérence au triage et à l'utilisation de mesures de protection personnelles. Les raisons majeures de la non-adhésion ont été le manque de fournitures appropriées, l'inconfort d'utilisation des masques N-95, le manque de connaissance ou de formation, la perception d'une non-coopération par les patients, la maintenance médiocre des ventilateurs mécaniques et de l'UVGI à cause de l'instabilité de l'alimentation électrique et le manque de clarification des responsabilités (aucune personne désignée responsable), et la pénurie de personnel avec surcharge de travail du personnel présent. L'adhésion à la ventilation naturelle a été médiocre en raison du climat et pour des problèmes de confidentialité.Conclusion : La mise en œuvre de mesures de CITB dans les hôpitaux a été sous-optimale. Des mesures urgentes sont requises, notamment la formation continue des HCW, la lutte contre les problèmes de fourniture de masques et d'affiches et une supervision et un suivi constants.

Marco de referencia: Diez hospitales que se ocupan del tratamiento de la tuberculosis (TB) multirresistente en el Pakistán.Objetivo: Evaluar la aplicación de las prácticas de control de la infección TB (CITB) y determinar las razones del incumplimiento de las normas.Método: De abril a octubre del 2016 se realizó un estudio descriptivo que comportó los siguientes elementos: 1) personas no vinculadas evaluaron las zonas de prestación de servicios (n = 82) en los hospitales (n = 10), con listas de verificación estructuradas; 2) se realizaron entrevistas de salida a 100 pacientes (10 por cada hospital) y 3) entrevistas a 100 profesionales de salud (HCW; 10 por cada hospital).Resultados: De las 82 zonas de prestación de servicios evaluadas, en 34 había afiches expuestos (41%), el 79% contaba con sistemas de ventilación mecánica y solo en el 26% existía un dispositivo funcional de radiación ultravioleta germicida (UVGI). Las entrevistas a los pacientes revelaron un cumplimiento de 50% a 65% con la selección de los pacientes y las medidas de protección personal. Las principales explicaciones del incumplimiento fueron la insuficiencia de suministros, la incomodidad de utilización de las mascarillas N-95, la carencia de conocimientos o capacitación adecuada, la percepción de una falta de cooperación por parte de los pacientes, un mantenimiento deficiente de los ventiladores mecánicos y los dispositivos de UVGI debido a la inestabilidad del suministro eléctrico y la poca claridad con respecto a las funciones (falta de designación de una persona encargada), la escasez de personal y la consecuente sobrecarga de trabajo. El cumplimiento de las normas de ventilación natural era deficiente por causa de las condiciones climáticas y aspectos relacionados con el respeto de la intimidad.Conclusión: La aplicación de las medidas de CITB en los hospitales es deficiente. Se precisa de manera urgente instaurar medidas como la actualización de la formación de los HCW, la corrección de las deficiencias en el abastecimiento de mascarillas y afiches y la práctica constante de la supervisión y la vigilancia.

Accuracy of Sentinel Node in Detecting Lymph Node Metastasis in Primary Endometrial Carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecological cancer and its treatment is still controversial, especially in its early stages. There are conflicting data about the efficacy of retroperitoneal lymphadenectomy during abdominal hysterectomy and bilateral salpingoophrectomy treatment. Lymphadenectomy carries a risk of severe complications, especially in women with co-morbidities. Selective lymphadenectomy has been widely employed for staging evaluation of endometrial carcinoma because it is simple and seems to provide reliable data regarding nodal metastasis. This study was designed to evaluate accuracy of sentinel node sampling in detecting lymph node metastasis in primary endometrial carcinoma during staging laparotomy. MATERIALS AND METHODS: Ninety-three women with endometrial carcinoma at high-risk for nodal metastasis were studied. During laparotomy, methylene blue dye was injected into sub-serosal myometrium, then retroperitoneal spaces were opened and blue lymph nodes within pelvic and para-aortic regions were removed as separate specimens for histopathological examination (sentinel lymph nodes=SLNs). Hysterectomy and selective lymphadenectomy then performed for all women included in this study. RESULTS: Deposition of methylene dye into at least one lymph node was observed in 73.1% (68/93) of studied cases. 18.3% (17/93) of studied women had positive lymph node metastasis and 94.1% (16/17) of them had positive metastasis in SLNs. In this study, SNLs had 94.4% sensitivity and 100% specificity in prediction of lymph node metastasis. Mean number of lymph nodes removed from each case decreased when SLNs biopsy were taken. CONCLUSIONS: SLNs are the key lymph nodes in endometrial tumor metastasis and their involvement could be an indicator for whether or not complete systematic lymphadenectomy is needed during staging laparotomy.