Effect of Oxidizers on Sulphide Removal from Hair Dissolving Liming Wastewater in Tannery

Liming and unhairing is the conventional operation in the tannery where raw animal skins are treated with sodium sulphide and calcium hydroxide to remove keratin proteins e.g., hair and wool epidermis and to dissolve nonstructural proteins. The hair dissolving liming process discharges wastewater containing soluble sulphide. In acidification, the sulphide in wastewater generates toxic hydrogen sulphide, which has a negative impact on the environment. In this present study, the efficiency of hydrogen peroxide (H2O2) and sodium chlorite (NaClO2) oxidizers are compared to remove sulphide from the hair dissolving liming wastewater. The soluble sulphide in the raw liming wastewater was 3666 mg/L. At optimized dose and pH for H2O2 and NaClO2 soluble sulphide in the solution were 109.2 and 54.6 mg/L, respectively. The sulphide removal efficiency for H2O2and NaClO2 were 97.0% and 98.5%, respectively at an optimum pH (pH 7). Before and after treatment the physicochemical parameters of the liming wastewater were analysed by observing different water quality parameters viz: pH, TDS, EC and salinity. At optimized condition TDS and salinity removal efficiency was 47.2%, 52.3% and 8.1%, 11.2% for H2O2 and NaClO2, respectively. This simple and easy method would be effective for treating hair dissolving liming wastewater in reducing soluble sulphide discharge from the tanneries. Journal of Engineering Science 12(3), 2021, 67-72

Review of Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine’s efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus’ genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune–epithelial interface

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2–specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach

The inhibition of key enzymes that may contain the viral replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have assumed central importance in drug discovery projects. Nonstructural proteins (nsps) are essential for RNA capping and coronavirus replication since it protects the virus from host innate immune restriction. In particular, nonstructural protein 16 (nsp16) in complex with nsp10 is a Cap-0 binding enzyme. The heterodimer formed by nsp16-nsp10 methylates the 5′-end of virally encoded mRNAs to mimic cellular mRNAs and thus it is one of the enzymes that is a potential target for antiviral therapy. In this study, we have evaluated the mechanism of the 2′-O methylation of the viral mRNA cap using hybrid quantum mechanics/molecular mechanics (QM/MM) approach. It was found that the calculated free energy barriers obtained at M062X/6-31+G(d,p) is in agreement with experimental observations. Overall, we provide a detailed molecular analysis of the catalytic mechanism involving the 2′-O methylation of the viral mRNA cap and, as expected, the results demonstrate that the TS stabilization is critical for the catalysis.

Chikungunya virus: Molecular epidemiology of nonstructural proteins in Pakistan

Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. In 2016–2017 an outbreak of CHIKV was occurred in Pakistan but the data regarding the genomic diversity of CHIKV was not reported. Hence, the current study aimed to determine the genetic diversity of CHIKVs in Pakistan. A cross sectional study was carried out using sera of infected CHIKV patients (n = 1549) during the outbreak in Pakistan (2016–2018). Nucleotide sequencing of non-structural genes of CHIKV from eight isolates were performed followed by phylogenetic analysis using Bayesian method. Phylogenetic analysis suggested that the Pakistani CHIKV strains belonged to Indian Ocean Lineage (IOL) of genotype ECSA and C1.3a clade. Furthermore, the Pakistani isolates showed several key mutations (nsP2-H130Y, nsP2-E145D, nsP4-S55N and nsP4- R85G) corresponding to mutations reported in 2016 Indian strains of CHIKV. The molecular analysis revealed high evolutionary potential of CHIKV strains as well as better understanding of enhanced virulence and pathogenesis of this outbreak. The study highlights the need to continue surveillance in order to understand viral diversity over time and to devise preventive measures to limit diseases transmission in the region.

Advances in the design and development of SARS-CoV-2 vaccines

Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials.

Selection of SARS-CoV-2 main protease inhibitor using structure-based virtual screening

Background: Conserved domains within SARS coronavirus 2 nonstructural proteins represent key targets for the design of novel inhibitors. Methods: The authors aimed to identify potential SARS coronavirus 2 NSP5 inhibitors using the ZINC database along with structure-based virtual screening and molecular dynamics simulation. Results: Of 13,840 compounds, 353 with robust docking scores were initially chosen, of which ten hit compounds were selected as candidates for detailed analyses. Three compounds were selected as coronavirus NSP5 inhibitors after passing absorption, distribution, metabolism, excretion and toxicity study; root and mean square deviation; and radius of gyration calculations. Conclusion: ZINC000049899562, ZINC000169336666 and ZINC000095542577 are potential NSP5 protease inhibitors that warrant further experimental studies.

Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backwards on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here, we use cryo-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results suggest a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.