An efficient computational protocol for template-based design of peptides that inhibit interactions involving SARS-CoV-2 proteins.

The RNA-dependent RNA polymerase (RdRp) complex of SARS-CoV-2 lies at the core of its replication and transcription processes. The interfaces between holo-RdRp subunits are highly conserved, facilitating the design of inhibitors with high affinity for the interaction interface hotspots. We, therefore, take this as a model protein complex for the application of a structural bioinformatics protocol to design peptides that inhibit RdRp complexation by preferential binding at the interface of its core subunit nonstructural protein, nsp12, with accessory factor nsp7. Here, the interaction hotspots of the nsp7-nsp12 subunit of RdRp, determined from a long molecular dynamics trajectory, are used as a template. A large library of peptide sequences constructed from multiple hotspot motifs of nsp12 is screened in-silico to determine sequences with high geometric complementarity and interaction specificity for the binding interface of nsp7 (target) in the complex. Two lead designed peptides are extensively characterized using orthogonal bioanalytical methods to determine their suitability for inhibition of RdRp complexation. Binding affinity of these peptides to accessory factor nsp7, determined using a surface plasmon resonance (SPR) assay, is slightly better than that of nsp12: dissociation constant of 133nM and 167nM, respectively, compared to 473nM for nsp12. A competitive ELISA is used to quantify inhibition of nsp7-nsp12 complexation, with one of the lead peptides giving an IC50 of 25µM . Cell penetrability and cytotoxicity are characterized using a cargo delivery assay and MTT cytotoxicity assay, respectively. Overall, this work presents a proof-of-concept of an approach for rational discovery of peptide inhibitors of SARS-CoV-2 protein-protein interactions.

Socio-Economic Analysis of the Construction and Building Materials' Usage—Ecological Awareness in the Case of Serbia

The main idea of the present study was to investigate the impact of the ongoing world crisis on the socio-economic issues in Serbia concerning building materials usage and purchase. This research fills in the gaps in the literature and contributes to the comprehension of how the crisis has affected salaries, market pricing, and materials consumption in the building sector. The data are gathered through a questionnaire and analyzed using a statistical methodology (frequencies, descriptive statistics, and Spearman's correlations). Most of the former studies investigated the surveys conducted on specialists in the field, while this study analyzed the perspectives of random people. Socio-demographic issues are analyzed along with materials consumption before and after the crisis. A special emphasis is given to ecological awareness and novel materials usage. Additionally, it captures a broad shift in the economy and ecological consciousness in a developing country. The majority of respondents are open to using novel building materials and products, but their choice would largely be influenced by cost, the amount of effort involved, and their understanding of the advantages. Statistical approaches revealed that the crisis has a considerable impact on the markets for construction and building supplies, altering consumers' decisions when purchasing. This contribution lays the groundwork for developing countries in the modern world to improve sustainability and adopt circular thinking. Professionals in Serbia need to have a more eco-aware mindset and enhance how they provide pertinent information to potential clients. This study is limited by the number of respondents. For future mathematical modeling and forecasting, more answerers are needed.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Hazardous giant pharyngoesophageal liposarcoma.

A man in his early 80s presented to the otorhinolaryngology department with progressively worsening dysphagia to solids and a recent episode of difficulty breathing accompanied by a very brief expulsion of a solid mass from the mouth. Based on the endoscopic appearance of a fatty lesion of an elongated mass with a thick stalk on the posterior pharyngeal wall, a diagnosis of the benign fibrovascular polyp was given after clinical and radiological correlation. The pharyngeal polyp was resected at the base of its pedicle by transoral endoscopy with a thunder beat vessel sealing device. Histopathological examination of the mass revealed a well-differentiated liposarcoma composed of mature adipocytes. Following surgical excision, the patient made a full recovery. This case signifies the integrated role of preoperative biopsy, new surgical technologies and targeted therapies in managing pharyngoesophageal polyps.

Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) in Delhi: Demographics and risk factors in a single-centre consecutive cohort of 200 inpatients.

Background There was a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis associated with the 2021 Covid-19 wave in India. We aim to document the demographic characteristics and risk factors of a consecutive cohort of inpatients with Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) during the surge of April-June 2021. Methods We included all patients of CAROM treated at our tertiary referral facility from 1 April to 14 June 2021. We prospectively gathered details with regard to Covid-19 illness and treatment, CAROM presentation, comorbid conditions and risk factors. Results Our prospective cohort consisted of 200 consecutive patients, of which 146 (73%) patients tested positive on the Covid-19 RT-PCR test at presentation. CAROM occurred concurrent with the Covid-19 infection in 86%, and delayed CAROM after seeming recovery from Covid-19 was seen in 14%. Covid-19 was classified as mild, moderate and severe in 54%, 33% and 13%. The surge of CAROM followed the population peak of Covid-19 infections by about 3 weeks. Advanced disease at presentation was frequent with ocular involvement in 56.6% (111/196) and central nervous system involvement in 20% (40/199). One or more comorbid conditions were identified in 191/200 (95.5%) patients. The dominant associations were with diabetes (189/200; 94.5%) and uncontrolled hyper-glycaemia (122/133; 91.7%), recent steroid use (114/ 200; 57%), which was often considered as inappropriate in dosage or duration, lymphopenia (142/176; 80.7%), and increased ferritin levels (140/160; 87.5%). No evidence supported the role of previous oxygen therapy or previous nasal swab testing as risk factors for CAROM. Conclusion The inpatient volumes of CAROM were noted to parallel the Covid-19 incidence curve by about 3 weeks. Covid-19 infection may directly predispose to CAROM by way of lymphopenia and increased ferritin levels. Uncontrolled hyperglycaemia is identified as a near-invariable association. Recent steroid use is noted as very frequent and was often received in excess of treatment advisories.

Using circular economy principles to recycle materials in guiding the design of a wet scrubber-reactor for indoor air disinfection from coronavirus and other pathogens.

An arduous need exists to discover rapid solutions to avoid the accelerated spread of coronavirus especially through the indoor environments like offices, hospitals, and airports. One such measure could be to disinfect the air, especially in indoor environments. The goal of this work is to propose a novel design of a wet scrubber-reactor to deactivate airborne microbes using circular economy principles. Based on Fenton's reaction mechanism, the system proposed here will deactivate airborne microbes (bioaerosols) such as SARS-CoV-2. The proposed design relies on using a highly porous clay-glass open-cell structure as an easily reproducible and cheap material. The principle behind this technique is an in-situ decomposition of hydrogen peroxide into highly reactive oxygen species and free radicals. The high porosity of a tailored ceramic structure provides a high contact area between atomized oxygen, free radicals and supplied polluted air. The design is shown to comply with the needs of achieving sustainable development goals.

COVID-19 and haematology services in a cancer centre from a middle-income country: adapting service delivery, balancing the known and unknown during the pandemic.

The COVID-19 pandemic has caused major disruptions in multiple spheres of healthcare delivery in the world. Developing nations have had to tackle this unanticipated crisis in the midst of various other healthcare delivery issues and resource constraints. As a tertiary level cancer care provider located in an eastern Indian city, a COVID-19 hotspot, we share our experience from the perspective of haematology and haematopoietic stem cell transplantation (HSCT) services. The primary challenges related to infection control included infection screening and decreasing exposure among patients and healthcare workers. Logistic challenges include maintaining essential patient care services, personnel redeployment, blood bank inventory constraints and maintaining the supply chain for a continuum of care. Clinical management challenges were dealt with by rationalising treatment delivery by modification of treatment regimens, risk-based deferral of HSCT, management of COVID-19 in patients, and staggering the follow-up schedules in survivors and those on maintenance therapies, among other strategies. These challenges were compounded by the restrictions imposed by a countrywide lockdown in the initial period of the pandemic, which also affected the socio-economic aspects of treatment delivery. As a training institution, this period also impacted academics and research activities. This overview details our response to these challenges during the COVID-19 pandemic, which has many unknowns.

The importance of intra- and inter-institutional networks for capacity building in severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction services: experience from an oncology centre in eastern India.

High-throughput, accurate, cost-effective and rapid testing for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the need of the hour in face of the global coronavirus disease pandemic. This target is achievable, within a relatively short time through capacity building of reverse transcription polymerase chain reaction (RT-PCR) tests by utilising the strengths of intra and inter institutional networks. These networks act as force multiplier for vital resources which are required for capacity building, namely, leadership, expertise, equipment, space, infection control inputs and human resources. In this article, we report the experience of capacity building for delivery of RT-PCR tests for SARS CoV-2 from a cancer hospital in Eastern India. The relevance, mode of operation and value addition of this essential public health service are discussed in the context of inter departmental collaboration and interaction with other institutes through the existing diagnostic, surveillance and infection control networks. This networking model for service development and delivery could be used by other centres.

Resilient and agile engineering solutions to address societal challenges such as coronavirus pandemic.

The world is witnessing tumultuous times as major economic powers including the US, UK, Russia, India, and most of Europe continue to be in a state of lockdown. The worst-hit sectors due to this lockdown are sales, production (manufacturing), transport (aerospace and automotive) and tourism. Lockdowns became necessary as a preventive measure to avoid the spread of the contagious and infectious "Coronavirus Disease 2019" (COVID-19). This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. We also offer perspectives on future considerations on climate change, outsourced versus indigenous manufacturing, automation, and antimicrobial resistance. Overall, this paper attempts to identify key areas where manufacturing can be employed to address societal challenges such as COVID-19.