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The COVID-19 crisis, incited by the zoonotic SARS-CoV-2 virus, has quickly escalated into a catastrophic public health issue and a grave threat to humankind owing to the advent of mutant viruses. Multiple pharmaceutical therapies or biologics envision stopping the virus from spreading further; however, WHO has voiced concerns about the variants of concern (VoCs) inability to respond. Nanobodies are a new class of antibody mimics with binding affinity and specificity similar to classical mAbs, as well as the privileges of a small molecular weight, ease of entry into solid tissues, and binding cryptic epitopes of the antigen. Herein, we investigated multiple putative anti-SARS-CoV-2 nanobodies targeting the Receptor binding domain of the WHO-listed SARS-CoV-2 variants of concern using a comprehensive computational immunoinformatics methodology. With affinity maturation via alanine scanning mutagenesis, we remodeled an ultrapotent nanobody with substantial breadth and potency, exhibiting pico-molar binding affinities against all the VoCs. An antiviral peptide with specificity for ACE-2 receptors was affixed to make it multispecific and discourage viral entry. Collectively, we constructed a broad-spectrum therapeutic biparatopic nanobody-peptide conjugate (NPC) extending coverage to SARS-CoV-2 VoCs RBDs. We PEGylated the biparatopic construct with 20kD maleimide-terminated PEG (MAL-(PEG)n-OMe) to improve its clinical efficacy limiting rapid renal clearance, and performed in silico cloning to facilitate future experimental studies. Our findings suggest that combining biparatopic nanobody conjugate with standard treatment may be a promising bivariate tool for combating viral entry during COVID-19 illness. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10570-x.

Work culture in Indian organizations has assumed a far greater significance in the context of the emerging business scenario. In order to gain and retain competitive advantage, it is imperative for organizations to develop a responsive work culture based on the new paradigm. An attempt has been made here to discern the direction of change, specify cultural imperatives, identify dimensions of responsive work culture and highlight their implications for organizations. Shifts in paradigm and corresponding changes in various dimensions of work culture have been suggested. In order to develop and reinforce responsive work culture in organizations, design and process imperatives have been outlined in brief.

Background and objectiveMultisystem inflammatory syndrome in children (MIS-C) is a postinfectious, generalized, hyperimmune state and is potentially lethal. There is scarce data on the clinical presentation and epidemiology of MIS-C in India. In light of this, we conducted this study to describe clinical presentations and outcomes in children diagnosed with MIS-C. MethodologyThis was a 15-month hospital-based prospective observational study conducted in the Departments of Pediatrics at Jagannath Hospital and Hitech Medical College, Bhubaneswar. The study included all patients diagnosed with MIS-C and treated at these hospitals between May 1, 2020, and August 31, 2021. The inclusion criteria were as follows: patients who were reverse transcription-polymerase chain reaction (RT-PCR)-positive, antibody-positive, or had known contact with those infected with coronavirus disease 2019 (COVID-19). We reviewed patient medical records to collect demographic data such as age, sex, body mass index (BMI), duration of illness, clinical symptomatology, findings of initial echocardiography, and outcomes. We followed each case for three months. We analyzed descriptive statistics using percentages and means and conducted the statistical analysis using SPSS Statistics for Windows, Version 25.0. (IBM Corp., Armonk, NY). ResultsA total of 30 cases were included in the study, consisting of 16 boys (53.3%) and 14 girls (46.7%). The mean age of the study population was 6.7 years, and 43% had a BMI in the overweight range. All patients (100%) had a fever, 66.7% had lethargy (n=20), and 64.3% (n=19) had abdominal symptoms in the form of vomiting, diarrhea, and abdominal pain. Respiratory distress at admission was found in 16 cases (53.3%), while hypotension at admission was found in 18 (60%) cases. Our population's average duration of pediatric ICU stay was 3.7 ± 1.2 days, and the average duration of inotropy was 2.2 ± 0.5 days. Fifteen cases (50%) required only oxygen support; 10 (33%) required noninvasive ventilation, and only one patient required invasive ventilation. Twenty-two patients (74%) needed fluid boluses. Outcomes of coronary artery dilatations were favorable, regressing to normal (Z-score <2.5) in affected patients within 90 days of follow-up. ConclusionsMIS-C has myriad presenting signs, symptoms, and severity. It is often associated with circulatory failure or shock. However, most patients demonstrated good early outcomes, improved left ventricle (LV) function, normalization of coronary abnormalities, and no mortality. This study provides additional data on the clinical presentation of MIS-C and highlights the importance of close, long-term follow-up monitoring of this patient population.