Identification of RdRp inhibitors against SARS-CoV-2 through E-pharmacophore-based virtual screening, molecular docking and MD simulations approaches.

The outbreak of novel Coronavirus, an enduring pandemic declared by WHO, has consequences to an alarming ongoing public health menace which has already claimed several million human lives. In addition to numerous vaccinations and medications for mild to moderate COVID-19 infection, lack of promising medication or therapeutic pharmaceuticals remains a serious concern to counter the ongoing coronavirus infections and to hinder its dreadful spread. Global health emergencies have called for urgency for potential drug discovery and time is the biggest constraint apart from the financial and human resources required for the high throughput drug screening. However, computational screening or in-silico approaches appeared to be an effective and faster approach to discover potential molecules without sacrificing the model animals. Accumulated shreds of evidence on computational studies against viral diseases have revealed significance of in-silico drug discovery approaches especially in the time of urgency. The central role of RdRp in SARS-CoV-2 replication makes it promising drug target to curtain on going infection and its spread. The present study aimed to employ E-pharmacophore-based virtual screening to reveal potent inhibitors of RdRp as potential leads to block the viral replication. An energy-optimised pharmacophore model was generated to screen the Enamine REAL DataBase (RDB). Then, ADME/T profiles were determined to validate the pharmacokinetics and pharmacodynamics properties of the hit compounds. Moreover, High Throughput Virtual Screening (HTVS) and molecular docking (SP & XP) were employed to screen the top hits from pharmacophore-based virtual screening and ADME/T screen. The binding free energies of the top hits were calculated by conducting MM-GBSA analysis followed by MD simulations to determine the stability of molecular interactions between top hits and RdRp protein. These virtual investigations revealed six compounds having binding free energies of -57.498, -45.776, -46.248, -35.67, -25.15 and -24.90 kcal/mol respectively as calculated by the MM-GBSA method. The MD simulation studies confirmed the stability of protein ligand complexes, hence, indicating as potent RdRp inhibitors and are promising candidate drugs to be further validated and translated into clinics in future.

Connecting SiO4 in Silicate and Silicate Chain Networks to Compute Kulli Temperature Indices.

A topological index is a numerical parameter that is derived mathematically from a graph structure. In chemical graph theory, these indices are used to quantify the chemical properties of chemical compounds. We compute the first and second temperature, hyper temperature indices, the sum connectivity temperature index, the product connectivity temperature index, the reciprocal product connectivity temperature index and the F temperature index of a molecular graph silicate network and silicate chain network. Furthermore, a QSPR study of the key topological indices is provided, and it is demonstrated that these topological indices are substantially linked with the physicochemical features of COVID-19 medicines. This theoretical method to find the temperature indices may help chemists and others in the pharmaceutical industry forecast the properties of silicate networks and silicate chain networks before trying.

Portable Electrochemical Biosensors Based on Microcontrollers for Detection of Viruses: A Review.

With the rise of zoonotic diseases in recent years, there is an urgent need for improved and more accessible screening and diagnostic methods to mitigate future outbreaks. The recent COVID-19 pandemic revealed an over-reliance on RT-PCR, a slow, costly and lab-based method for diagnostics. To better manage the pandemic, a high-throughput, rapid point-of-care device is needed for early detection and isolation of patients. Electrochemical biosensors offer a promising solution, as they can be used to perform on-site tests without the need for centralized labs, producing high-throughput and accurate measurements compared to rapid test kits. In this work, we detail important considerations for the use of electrochemical biosensors for the detection of respiratory viruses. Methods of enhancing signal outputs via amplification of the analyte, biorecognition of elements and modification of the transducer are also explained. The use of portable potentiostats and microfluidics chambers that create a miniature lab are also discussed in detail as an alternative to centralized laboratory settings. The state-of-the-art usage of portable potentiostats for detection of viruses is also elaborated and categorized according to detection technique: amperometry, voltammetry and electrochemical impedance spectroscopy. In terms of integration with microfluidics, RT-LAMP is identified as the preferred method for DNA amplification virus detection. RT-LAMP methods have shorter turnaround times compared to RT-PCR and do not require thermal cycling. Current applications of RT-LAMP for virus detection are also elaborated upon.

Virtual curriculum delivery in the COVID-19 era: the pediatric surgery boot camp v2.0.

PURPOSE: We evaluated the impact of a virtual Pediatric Surgery Bootcamp curriculum on resource utilization, learner engagement, knowledge retention, and stakeholder satisfaction. METHODS: A virtual curriculum was developed around Pediatric Surgery Milestones. GlobalCastMD delivered pre-recorded and live content over a single 10-h day with a concluding social hour. Metrics of learner engagement, faculty interaction, knowledge retention, and satisfaction were collected and analyzed during and after the course. RESULTS: Of 56 PS residencies, 31 registered (55.4%; 8/8 Canadian and 23/48 US; p = 0.006), including 42 learners overall. The virtual BC budget was $15,500 (USD), 54% of the anticipated in-person course. Pre- and post-tests were administered, revealing significant knowledge improvement (48.6% [286/589] vs 66.9% [89/133] p < 0.0002). Learner surveys (n = 14) suggested the virtual BC facilitated fellowship transition (85%) and strengthened peer-group camaraderie (69%), but in-person events were still favored (77%). Program Directors (PD) were surveyed, and respondents (n = 22) also favored in-person events (61%). PDs not registering their learners (n = 7) perceived insufficient value-added and concern for excessive participants. CONCLUSIONS: The virtual bootcamp format reduced overall expenses, interfered less with schedules, achieved more inclusive reach, and facilitated content archiving. Despite these advantages, learners and program directors still favored in-person education. LEVEL OF EVIDENCE: III.

Association between COVID-19 related elective surgery cancellations and pediatric inguinal hernia complications: A nationwide multicenter cohort study.

BACKGROUND: Optimal inguinal hernia repair timing remains controversial. It remains unclear how COVID-19 related elective surgery cancellations impacted timing of inguinal hernia repair and whether any delays led to complications. This study aims to determine whether elective surgery cancellations are safe in pediatric inguinal hernia. METHODS: This multicenter retrospective cohort study at 14 children's hospitals included patients ≤18 years who underwent inguinal hernia repair between September 13, 2019, through September 13, 2020. Patients were categorized by whether their inguinal hernia repair occurred before or after their hospital's COVID-19 elective surgery cancellation date. Incarceration and emergency department encounters were compared between pre and postcancellation. RESULTS: Of 1,404 patients, 604 (43.0%) underwent inguinal hernia repair during the postcancellation period, 92 (6.6%) experienced incarceration, and 213 (15.2%) had an emergency department encounter. The postcancellation period was not associated with incarceration (odds ratio 1.54; 95% confidence interval 0.88-2.71; P = .13) or emergency department encounters (odds ratio 1.53; 95% confidence interval 0.94-2.48; P = .09) despite longer median times to inguinal hernia repair (precancellation 29 days [interquartile range 13-55 days] versus postcancellation 31 days [interquartile range 14-73 days], P = .01). Infants were more likely to have the emergency department be their index presentation in the postcancellation period (odds ratio 1.69; 95% confidence interval 1.24-2.31; P < .01). CONCLUSION: Overall, COVID-19 elective surgery cancellations do not appear to increase the likelihood of incarceration or emergency department encounters despite delays in inguinal hernia repair, suggesting that cancellations are safe in children with inguinal hernia. Assessment of elective surgery cancellation safety has important implications for health policy.

Post COVID-19 Sino-Orbital Mucormycosis: A Therapeutic Challenge

Objective: To determine the frequency of sino-orbital mucormycosis outcomes in diagnosed patients of COVID-19 and its association with the duration of the disease. Study Design: Case series. Place and Duration of Study: Armed Forces Institute of Ophthalmology, Pak Emirates Military Hospital, Rawalpindi, from Feb to Jul 2021. Methodology: A sample size of 20 was calculated using WHO calculator. Diagnosed patients of COVID-19 who fulfilled the inclusion criteria were selected through consecutive sampling technique. The mode of presentation, in-depth imaging findings, associated co-morbidities and management/follow up details were collected. Results: Total 20 patients were included in study. There were 12 (60%) male and 8 (40%) female. Mean age of patients was 60.4 ± 9.8 years. Outcomes of study were treatment, still of follow up, mortality and mortality with sepsis, survival and exenteration (15%, 15%, 25%, 5%, 25% 15% respectively). Among all the patients, 2(10%) patients showed intraconal and extraconal orbital involvement, 9 (45%) showed left, 8 (40%) showed right and 1(5%) showed both orbits involvement. Outcomes of sino-orbital mucormycosis showed significant association with COVID-19 duration (p=0.03). Conclusion: Sino-Orbital mucormycosis is a common and potentially life-threatening complication of COVID-19. Early initiation of anti-fungal treatment as well as surgical intervention are key to decrease both the mortality and morbidity associated with the disease.

SARS-CoV-2 Testing of Aerosols Emitted During Pediatric Minimally Invasive Surgery: A Prospective, Case-Controlled Study.

BACKGROUND: The COVID-19 pandemic has presented significant safety concerns for healthcare providers, especially those performing aerosol-generating procedures. Several surgical societies issued early warnings that aerosols generated during minimally invasive surgery (MIS) could harbor infectious quantities of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study tested the hypothesis that MIS-aerosols contain SARS-CoV-2. METHODS: To evaluate SARS-CoV-2 presence in aerosols emitted during intracavitary MIS, children <18 years who required emergent MIS and were discovered to be SARS-CoV-2-positive were enrolled. Swabs were obtained from the port in-line with a filtered smoke evacuation system, the tubing adjacent to this port, the fluid collection chamber and filter, and the distal endotracheal tube (ETT). All swabs were analyzed for SARS-CoV-2 using quantitative reverse-transcription polymerase chain reaction. To evaluate viral distribution in tissues, fluorescence in situ hybridization for SARS-CoV-2 was performed on resected specimens. Outcomes were recorded, and participating healthcare workers were tracked for SARS-CoV-2 conversion. RESULTS: From July 1, 2020, to June 30, 2021, 11 children requiring emergent MIS were discovered preoperatively to be SARS-CoV-2 positive (median age: 14 years [5-17]). SARS-CoV-2 was detected only in ETT swabs and not in surgical aerosols or specimens. Median operative time was 56.5 minutes (IQR: 46-66), and postoperative stay was 21.2 hours (IQR: 1.97-57.57). No complications or viral eruption were recorded, and none of 63 healthcare workers tested positive for SARS-CoV-2 within 6 weeks. DISCUSSION: SARS-CoV-2 was detected only in ETT secretions and not in surgical aerosols or specimens among a pediatric cohort of asymptomatic patients having emergent MIS.

Deep Ensemble Model for Classification of Novel Coronavirus in Chest X-Ray Images.

The novel coronavirus, SARS-CoV-2, can be deadly to people, causing COVID-19. The ease of its propagation, coupled with its high capacity for illness and death in infected individuals, makes it a hazard to the community. Chest X-rays are one of the most common but most difficult to interpret radiographic examination for early diagnosis of coronavirus-related infections. They carry a considerable amount of anatomical and physiological information, but it is sometimes difficult even for the expert radiologist to derive the related information they contain. Automatic classification using deep learning models can help in better assessing these infections swiftly. Deep CNN models, namely, MobileNet, ResNet50, and InceptionV3, were applied with different variations, including training the model from the start, fine-tuning along with adjusting learned weights of all layers, and fine-tuning with learned weights along with augmentation. Fine-tuning with augmentation produced the best results in pretrained models. Out of these, two best-performing models (MobileNet and InceptionV3) selected for ensemble learning produced accuracy and FScore of 95.18% and 90.34%, and 95.75% and 91.47%, respectively. The proposed hybrid ensemble model generated with the merger of these deep models produced a classification accuracy and FScore of 96.49% and 92.97%. For test dataset, which was separately kept, the model generated accuracy and FScore of 94.19% and 88.64%. Automatic classification using deep ensemble learning can help radiologists in the correct identification of coronavirus-related infections in chest X-rays. Consequently, this swift and computer-aided diagnosis can help in saving precious human lives and minimizing the social and economic impact on society.

Intracranial hemorrhage complicating anticoagulant prophylactic therapy in three hospitalized COVID-19 patients.

SARS-CoV2 has led to a global pandemic affecting almost 3 million people in almost over 3 months. Various clinical presentations have been reported so far and no definite therapy is established. Anticoagulation is recommended by several experts to address the potential prothrombotic complications from COVID-19, but its safety and regimen need further clinical trials and safety and efficacy profile. Here, we present three cases of intracranial hemorrhage in three critically ill patients with COVID-19 and discuss their course in relation to various regimens of anticoagulation used.