Post-acute sequelae of SARS-CoV-2 Delta variant infection: A report of three cases in a single family

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has resulted in global pandemic and crisis in health care system. Several studies have focused only on hospitalized patients with 30 to 90 days after one cycle of illness but post-acute sequelae of COVID-19 existing even after a year remains unclear. Moreover, long-term sequelae in outpatients have not been documented and henceforth myriad clinical sequelae in long haulers continue to evolve. In this study, we report three cases represents a single family presenting several post-acute sequelae one after the other extending beyond one year of recovery. To our knowledge such a case series has not been reported in earlier studies. Herein, we present the sequelae in various organs namely neuropsychiatric (tinnitus, anxiety, depression, insomnia, and posttraumatic stress disorder, cognitive decline), cardiovascular (tachycardia, bradycardia), gastrointestinal (appendicitis) and Dermatologic (erythematous rash and acne) besides ophthalmic manifestations (conjunctivitis and dry eyes) in Long-COVID-19 and recommend management strategies

Computer-Aided vaccine design for selected positive-sense single stranded RNA viruses

Spontaneous mutations and lack of replication fidelity in positive-sense single stranded RNA viruses (+ssRNA virus) result in emergence of genetic variants with diverse viral morphogenesis and surface proteins that affect its antigenicity. This high mutability in +ssRNA viruses has induced antiviral drug resistance and ability to overcome vaccines that subsequently resulted in rapid viral evolution and high mortality rate in human and livestock. Computer aided vaccine design and immunoinformatics play a crucial role in expediting the vaccine production protocols, antibody production and identifying suitable immunogenic regions or epitopes from the genome sequences of the pathogens. T cell and B cell epitopes can be identified in pathogens by immunoinformatics algorithms and methods that enhance the analysis of protective immunity, vaccine safety, immunity modelling and vaccine efficacy. This rapid and cost-effective computational vaccine design promotes development of potential vaccine that could induce immune response in host against rapidly mutating pathogens like +ssRNA viruses. Epitope-based vaccine is a striking concept that has been widely employed in recent years to construct vaccines targeting rapidly mutating +ssRNA viruses. Therefore, the present review provides an overview about the current progress and methodology in computer-aided vaccine design for the most notable +ssRNA viruses namely Hepatitis C virus, Dengue virus, Chikungunya virus and Coronaviruses. This review also highlights the applications of various immunoinformatics tools for vaccine design and for modelling immune response against +ssRNA viruses

Structural Determination of Functional Units of the Nucleotide Binding Domain (NBD94) of the Reticulocyte Binding Protein Py235 of Plasmodium yoelii

Invasion of the red blood cells (RBC) by the merozoite of malaria parasites involves a large number of receptor ligand interactions. The reticulocyte binding protein homologue family (RH) plays an important role in erythrocyte recognition as well as virulence. Recently, it has been shown that members of RH in addition to receptor binding may also have a role as ATP/ADP sensor. A 94 kDa region named Nucleotide-Binding Domain 94 (NBD94) of Plasmodium yoelii YM, representative of the putative nucleotide binding region of RH, has been demonstrated to bind ATP and ADP selectively. Binding of ATP or ADP induced nucleotide-dependent structural changes in the C-terminal hinge-region of NBD94, and directly impacted on the RBC binding ability of RH.In order to find the smallest structural unit, able to bind nucleotides, and its coupling module, the hinge region, three truncated domains of NBD94 have been generated, termed NBD94(444-547), NBD94(566-663) and NBD94(674-793), respectively. Using fluorescence correlation spectroscopy NBD94(444-547) has been identified to form the smallest nucleotide binding segment, sensitive for ATP and ADP, which became inhibited by 4-Chloro-7-nitrobenzofurazan. The shape of NBD94(444-547) in solution was calculated from small-angle X-ray scattering data, revealing an elongated molecule, comprised of two globular domains, connected by a spiral segment of about 73.1 A in length. The high quality of the constructs, forming the hinge-region, NBD94(566-663) and NBD94(674-793) enabled to determine the first crystallographic and solution structure, respectively. The crystal structure of NBD94(566-663) consists of two helices with 97.8 A and 48.6 A in length, linked by a loop. By comparison, the low resolution structure of NBD94(674-793) in solution represents a chair-like shape with three architectural segments.These structures give the first insight into how nucleotide binding impacts on the overall structure of RH and demonstrates the potential use of this region as a novel drug target

Green synthesis of silver nanoparticles using Lippia nodiflora aerial extract and evaluation of their antioxidant, antibacterial and cytotoxic effects

Silver nanoparticles biosynthesis has received increasing attention in the field of nanotechnology due to their antimicrobial and biomedical applications. Green synthesis of metal nanoparticles is anticipated as a cost effective and eco-friendly alternative in the current research scenario. With this aim, the aqueous extracts made from the aerial parts of Lippia nodiflora were used as the reducing agents to synthesize silver nanoparticles (AgNPs) and their antioxidant, antibacterial and cytotoxic properties have also been evaluated. The biosynthesized AgNPs were characterized by UVâVisible Spectroscopy, Fourier-Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD) analysis. The AgNPs were found to be stable at â25.2â¯mV through zeta potential study. The morphology and size of synthesized silver nanoparticles were confirmed by Scanning Electron Microscope with energy dispersive spectra (SEM-EDX) and Transmission Electron Microscopy (TEM) analysis with size range from 30 to 60â¯nm. Biosynthesized AgNPs exhibited strong antioxidant activity as well as showed potent antibacterial activity against human pathogenic bacteria. The cytotoxicity study of AgNPs was also revealed against MCF-7 breast cancer cell lines in a dose-dependent manner. The recognized bioactivity confirmed by the synthesized AgNPs directs towards the clinical use as an antioxidant, antibacterial and cytotoxic agent. Keywords: Lippia nodiflora, Silver nanoparticles, SEM, Antioxidant, Antibacterial, Cytotoxicit

Post-acute sequelae of SARS-CoV-2 Delta variant infection: A report of three cases in a single family

777-785Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has resulted in global pandemic and crisis in health care system. Several studies have focused only on hospitalized patients with 30 to 90 days after one cycle of illness but post-acute sequelae of COVID-19 existing even after a year remains unclear. Moreover, long-term sequelae in outpatients have not been documented and henceforth myriad clinical sequelae in long haulers continue to evolve. In this study, we report three cases represents a single family presenting several post-acute sequelae one after the other extending beyond one year of recovery. To our knowledge such a case series has not been reported in earlier studies. Herein, we present the sequelae in various organs namely neuropsychiatric (tinnitus, anxiety, depression, insomnia, and posttraumatic stress disorder, cognitive decline), cardiovascular (tachycardia, bradycardia), gastrointestinal (appendicitis) and Dermatologic (erythematous rash and acne) besides ophthalmic manifestations (conjunctivitis and dry eyes) in Long-COVID-19 and recommend management strategies

Catalytic pathway, substrate binding and stability in SAICAR synthetase: A structure and molecular dynamics study

The de novo purine biosynthesis is one of the highly conserved pathways among all organisms and is essential for the cell viability. A clear understanding of the enzymes in this pathway would pave way for the development of antimicrobial and anticancer drugs. Phosphoribosylaminoimidazole-succinocar boxamide (SAICAR) synthetase is one of the enzymes in this pathway that catalyzes ATP dependent ligation of carboxyaminoimidazole ribotide (CAIR) with L-aspartate (ASP). Here, we describe eight crystal structures of this enzyme, in C222(1) and H3 space groups, bound to various substrates and substrate mimics from a hyperthermophilic archaea Pyrococcus horikoshii along with molecular dynamics simulations of the structures with substrates. Complexes exhibit minimal deviation from its apo structure. The CAIR binding site displays a preference for pyrimidine nucleotides. In the ADP.TMP-ASP complex, the ASP binds at a position equivalent to that found in Saccharomyces cerevisiae structure (PDB: 2CNU) and thus, clears the ambiguity regarding ASP's position. A possible mode for the inhibition of the enzyme by CTP and UTP, observed earlier in the yeast enzyme, is clearly illustrated in the structures bound to CMP and UMP. The ADP.Mg2+.PO4.CD/MP complex having a phosphate ion between the ATP and CAIR sites strengthens one of the two probable pathways (proposed in Escherichia coli study) of catalytic mechanism and suggests the possibility of a phosphorylation taking place before the ASP's attack on CAIR. Molecular dynamic simulations of this enzyme along with its substrates at 90 degrees C reveal the relative strengths of substrate binding, possible antagonism and the role of Mg2+ ions. (C) 2015 Elsevier Inc. All rights reserved