Substantial Changes in Selected Volatile Organic Compounds (VOCs) and Associations with Health Risk Assessments in Industrial Areas during the COVID-19 Pandemic.

During the COVID-19 pandemic, governments in many countries worldwide, including India, imposed several restriction measures, including lockdowns, to prevent the spread of the infection. COVID-19 lockdowns led to a reduction in gaseous and particulate pollutants in ambient air. In the present study, we investigated the substantial changes in selected volatile organic compounds (VOCs) after the outbreak of the coronavirus pandemic and associations with health risk assessments in industrial areas. VOC data from 1 January 2019 to 31 December 2021 were collected from the Central Pollution Control Board (CPCB) website, to identify percentage changes in VOC levels before, during, and after COVID-19. The mean TVOC levels at all monitoring stations were 47.22 ± 30.15, 37.19 ± 37.19, and 32.81 ± 32.81 µg/m3 for 2019, 2020, and 2021, respectively. As a result, the TVOC levels gradually declined in consecutive years due to the pandemic in India. The mean TVOC levels at all monitoring stations declined from 9 to 61% during the pandemic period as compared with the pre-pandemic period. In the current study, the T/B ratio values ranged from 2.16 (PG) to 26.38 (NL), which indicated that the major pollutant contributors were traffic and non-traffic sources during the pre-pandemic period. The present findings indicated that TVOC levels had positive but low correlations with SR, BP, RF, and WD, with correlation coefficients (r) of 0.034, 0.118, 0.012, and 0.007, respectively, whereas negative correlations were observed with AT and WS, with correlation coefficients (r) of -0.168 and -0.150, respectively. The lifetime cancer risk (LCR) value for benzene was reported to be higher in children, followed by females and males, for the pre-pandemic, pandemic, and post-pandemic periods. A nationwide scale-up of this study's findings might be useful in formulating future air pollution reduction policies associated with a reduction in health risk factors. Furthermore, the present study provides baseline data for future studies on the impacts of anthropogenic activities on the air quality of a region.

Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors.

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of -10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤-8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of -61.42 kcal/mol and -61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = -53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.

In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea.

Hypericum perforatum and Echinacea are reported to have antiviral activities against several viral infections. In this study, H. perforatum (St. John's Wort) and Echinacea were tested in vitro using Vero E6 cells for their anti-viral effects against the newly identified Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) through its infectious cycle from 0 to 48 h post infection. The hypericin of H. perforatum and the different parts (roots, seeds, aerial) of two types of Echinacea species (Echinacea purpurea and Echinacea angustifolia) were tested for their anti-viral activities to measure the inhibition of viral load using quantitative real-time polymerase chain reaction (qRT-PCR) on cell culture assay. Interestingly, the H. perforatum-Echinacea mixture (1:1 ratio) of H. perforatum and Echinacea was tested as well on SARS-CoV-2 and showed crucial anti-viral activity competing H. perforatum then Echinacea effects as anti-viral treatment. Therefore, the results H. perforatum and Echinacea species, applied in this study showed significant anti-viral and virucidal effects in the following order of potency: H. perforatum, H. perforatum-Echinacea mixture, and Echinacea on SARS-CoV-2 infectious cycle. Additionally, molecular simulation analysis of the compounds with essential proteins (Mpro and RdRp) of the SARS-CoV-2 revealed the most potent bioactive compounds such as Echinacin, Echinacoside, Cyanin, Cyanidin 3-(6''-alonylglucoside, Quercetin-3-O-glucuronide, Proanthocyanidins, Rutin, Kaempferol-3-O-rutinoside, and Quercetin-3-O-xyloside. Thus, based on the outcome of this study, it is demanding the setup of clinical trial with specific therapeutic protocol.

Genomic profiling and network-level understanding uncover the potential genes and the pathways in hepatocellular carcinoma.

Data integration with phenotypes such as gene expression, pathways or function, and protein-protein interactions data has proven to be a highly promising technique for improving human complex diseases, particularly cancer patient outcome prediction. Hepatocellular carcinoma is one of the most prevalent cancers, and the most common cause is chronic HBV and HCV infection, which is linked to the majority of cases, and HBV and HCV play a role in multistep carcinogenesis progression. We examined the list of known hepatocellular carcinoma biomarkers with the publicly available expression profile dataset of hepatocellular carcinoma infected with HCV from day 1 to day 10 in this study. The study covers an overexpression pattern for the selected biomarkers in clinical hepatocellular carcinoma patients, a combined investigation of these biomarkers with the gathered temporal dataset, temporal expression profiling changes, and temporal pathway enrichment following HCV infection. Following a temporal analysis, it was discovered that the early stages of HCV infection tend to be more harmful in terms of expression shifting patterns, and that there is no significant change after that, followed by a set of genes that are consistently altered. PI3K, cAMP, TGF, TNF, Rap1, NF-kB, Apoptosis, Longevity regulating pathway, signaling pathways regulating pluripotency of stem cells, Cytokine-cytokine receptor interaction, p53 signaling, Wnt signaling, Toll-like receptor signaling, and Hippo signaling pathways are just a few of the most commonly enriched pathways. The majority of these pathways are well-known for their roles in the immune system, infection and inflammation, and human illnesses like cancer. We also find that ADCY8, MYC, PTK2, CTNNB1, TP53, RB1, PRKCA, TCF7L2, PAK1, ITPR2, CYP3A4, UGT1A6, GCK, and FGFR2/3 appear to be among the prominent genes based on the networks of genes and pathways based on the copy number alterations, mutations, and structural variants study.

Role of hepatitis c virus in hepatocellular carcinoma and neurological disorders: an overview.

The hepatitis C virus (HCV) causes serious issues, affecting 71 million people globally. The most common manifestations range from chronic hepatitis to liver cirrhosis, leading to hepatocellular carcinoma. Many mechanisms are known to play an important role in HCV-induced HCC. The interaction of viral proteins with host cells results in oxidative stress damage, liver inflammation, and irregularities in signaling pathways. These results in the activation of oncogenes and metabolic disturbances, liver fibrosis, and angiogenesis. Additionally, some non-coding RNAs (ncRNAs) and toll-like receptors have been identified and play a significant role in HCC development. This virus is also associated with impairment of the central nervous system, resulting in acute or sub-acute encephalopathy and inflammatory disorders. Neurological disorders are associated with the inflammatory responses of many cells, including microglia and astrocytes. Additionally, there are many other extrahepatic manifestations, including neurological disorders such as depression and fatigue, in 50% of infected patients. These manifestations include neuro-invasion, immune-mediated damage, neurotransmitter alterations, sensory-motor polyneuropathy, sensitivity loss, weakness of the leg, and cryoglobulinemia, which significantly results in a reduced quality of life. HCV infection may be improved using an appropriate diagnosis and direct antiviral therapy for sustained virological response. However, the success of therapy depends on the symptoms and organ damage, diagnosis, and therapeutic strategies applied. Some published reports have discussed that HCV is associated with both HCC and neurological disorders. Additionally, it has also been observed that individuals with HCC also develop neurological disorders compared with individuals with HCV alone. This review aims to provide an overview of the latest information about the relationship between HCV-induced HCC and their role in neurological disorders. Additionally, we have also discussed the progress made in the diagnosis, physio-pathological mechanisms, and strong antiviral therapies developed for HCV infection and HCC, as well as the latest advancements made in the study of the neurological disorders associated with HCV infection.

SARS-CoV-2 Mpro inhibitors: identification of anti-SARS-CoV-2 Mpro compounds from FDA approved drugs.

Recent outbreak of COVID-19 pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has raised serious global concern for public health. The viral main 3-chymotrypsin-like cysteine protease (Mpro), known to control coronavirus replication and essential for viral life cycle, has been established as an essential drug discovery target for SARS-CoV-2. Herein, we employed computationally screening of Druglib database containing FDA approved drugs against active pocket of SARS-CoV-2 Mpro using MTiopen screen web server, yields a total of 1051 FDA approved drugs with docking energy >-7 kcal/mol. The top 10 screened potential compounds against SARS-CoV-2 Mpro were then studied by re-docking, binding affinity, intermolecular interaction, and complex stability via 100 ns all atoms molecular dynamics (MD) simulation followed by post-simulation analysis, including end point binding free energy, essential dynamics, and residual correlation analysis against native crystal structure ligand N3 inhibitor. Based on comparative molecular simulation and interaction profiling of the screened drugs with SARS-CoV-2 Mpro revealed R428 (-10.5 kcal/mol), Teniposide (-9.8 kcal/mol), VS-5584 (-9.4 kcal/mol), and Setileuton (-8.5 kcal/mol) with stronger stability and affinity than other drugs and N3 inhibitor; and hence, these drugs are advocated for further validation using in vitro enzyme inhibition and in vivo studies against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.

Understanding the role of potential pathways and its components including hypoxia and immune system in case of oral cancer.

There are a few biological functions or phenomenon which are universally associated with majority of the cancers and hypoxia and immune systems are among them. Hypoxia often occurs in most of the cancers which helps the cells in adapting different responses with respect to the normal cells which may be the activation of signaling pathways which regulate proliferation, angiogenesis, and cell death. Similar to it, immune signaling pathways are known to play critical roles in cancers. Moreover, there are a number of genes which are known to be associated with these hypoxia and immune system and appear to direct affect the tumor growth and propagations. Cancer is among the leading cause of death and oral cancer is the tenth-leading cause due to cancer death. In this study, we were mainly interested to understand the impact of alteration in the expression of hypoxia and immune system-related genes and their contribution to head and neck squamous cell carcinoma. Moreover, we have collected the genes associated with hypoxia and immune system from the literatures. In this work, we have performed meta-analysis of the gene and microRNA expression and mutational datasets obtained from public database for different grades of tumor in case of oral cancer. Based on our results, we conclude that the critical pathways which dominantly enriched are associated with metabolism, cell cycle, immune system and based on the survival analysis of the hypoxic genes, we observe that the potential genes associated with head and neck squamous cell carcinoma and its progression are STC2, PGK1, P4HA1, HK1, SPIB, ANXA5, SERPINE1, HGF, PFKM, TGFB1, L1CAM, ELK4, EHF, and CDK2.

Isolation of Yasminevirus, the First Member of Klosneuvirinae Isolated in Coculture with Vermamoeba vermiformis, Demonstrates an Extended Arsenal of Translational Apparatus Components.

The family of giant viruses is still expanding, and evidence of a translational machinery is emerging in the virosphere. The Klosneuvirinae group of giant viruses was first reconstructed from in silico studies, and then a unique member was isolated, Bodo saltans virus. Here we describe the isolation of a new member in this group using coculture with the free-living amoeba Vermamoeba vermiformis This giant virus, called Yasminevirus, has a 2.1-Mb linear double-stranded DNA genome encoding 1,541 candidate proteins, with a GC content estimated at 40.2%. Yasminevirus possesses a nearly complete translational machinery, with a set of 70 tRNAs associated with 45 codons and recognizing 20 amino acids (aa), 20 aminoacyl-tRNA synthetases (aaRSs) recognizing 20 aa, as well as several translation factors and elongation factors. At the genome scale, evolutionary analyses placed this virus in the Klosneuvirinae group of giant viruses. Rhizome analysis demonstrated that the genome of Yasminevirus is mosaic, with ∼34% of genes having their closest homologues in other viruses, followed by ∼13.2% in Eukaryota, ∼7.2% in Bacteria, and less than 1% in Archaea Among giant virus sequences, Yasminevirus shared 87% of viral hits with Klosneuvirinae. This description of Yasminevirus sheds light on the Klosneuvirinae group in a captivating quest to understand the evolution and diversity of giant viruses.IMPORTANCE Yasminevirus is an icosahedral double-stranded DNA virus isolated from sewage water by amoeba coculture. Here its structure and replicative cycle in the amoeba Vermamoeba vermiformis are described and genomic and evolutionary studies are reported. This virus belongs to the Klosneuvirinae group of giant viruses, representing the second isolated and cultivated giant virus in this group, and is the first isolated using a coculture procedure. Extended translational machinery pointed to Yasminevirus among the quasiautonomous giant viruses with the most complete translational apparatus of the known virosphere.

Detection of genetic alterations in gastric cancer patients from Saudi Arabia using comparative genomic hybridization (CGH).

BACKGROUND: The present study was conducted to discover genetic imbalances such as DNA copy number variations (CNVs) associated with gastric cancer (GC) and to examine their association with different genes involved in the process of gastric carcinogenesis in Saudi population. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues samples from 33 gastric cancer patients and 15 normal gastric samples were collected. Early and late stages GC samples were genotyped and CNVs were assessed by using Illumina HumanOmni1-Quad v.1.0 BeadChip. RESULTS: Copy number gains were more frequent than losses throughout all GC samples compared to normal tissue samples. The mean number of the altered chromosome per case was 64 for gains and 40 for losses, and the median aberration length was 679115bp for gains and 375889bp for losses. We identified 7 high copy gain, 52 gains, 14 losses, 32 homozygous losses, and 10 copy neutral LOHs (loss of heterozygosities). Copy number gains were frequently detected at 1p36.32, 1q12, 1q22, 2p11.1, 4q23-q25, 5p12-p11, 6p21.33, 9q12-q21.11, 12q11-q12, 14q32.33, 16p13.3, 17p13.1, 17q25.3, 19q13.32, and losses at 1p36.23, 1p36.32, 1p32.1, 1q44, 3q25.2, 6p22.1, 6p21.33, 8p11.22, 10q22.1, 12p11.22, 14q32.12 and 16q24.2. We also identified 2 monosomy at chromosome 14 and 22, 52 partially trisomy and 22 whole chromosome 4 neutral loss of heterozygosities at 13q14.2-q21.33, 5p15.2-p15.1, 5q11.2-q13.2, 5q33.1-q34 and 3p14.2-q13.12. Furthermore, 11 gains and 2 losses at 1p36.32 were detected for 11 different GC samples and this region has not been reported before in other populations. Statistical analysis confirms significant association of H. pylori infection with T4 stage of GC as compare to control and other stages. CONCLUSIONS: We found that high frequency of copy number gains and losses at 1p36.23, 1p32.1, 1p36.32, 3q25.2, 6p21.33 and 16q24.2 may be common events in gastric cancer. While novel CNVs at 1p36.32 harbouring PRDM16, TP73 and TP73-AS1 genes showed 11 gains and 2 losses for 11 different GC cases and this region is not reported yet in Database of Genomic Variants may be specific to Saudi population.

Analysis of Hepatitis B virus (HBV) mutations in patients from Western Saudi Arabia with chronic disease.

INTRODUCTION: Extensive research has provided a link between HBV variants and the clinical complications of liver diseases. This study was performed to further investigate the relationship between HBV variants in preS, S and BCP/PC regions and disease progression in chronic hepatitis B (CHB) cases in Jeddah, Saudi Arabia. METHODOLOGY: 182 CHB patients were recruited for this study. HBV DNA was amplified by PCR in the PreS, S, and BCP/PC regions. Sequences were generated from 31 and 26 treated cases in PreS and S regions respectively and from 72 cases in the BCP/PC region. RESULTS: The majority of cases (86.7%) were genotype D. Mutations at preS1-A2922C, X-A1624C and PC-G1887A were detected only in cases with either a high fibrosis score or hepatocellular carcinoma (HCC), while mutations at positions PC-C1982A, PC-G1951T, X-C1628T and X-A1630G were detected more frequently in HCC cases, without reaching statistical significance. Seven deletions were detected in the PreS-region. No deletions were detected in the CCAAT box. The accumulation of mutations per sample in the preS1-2 and S regions were associated with elevated ALT (p < 0.001, 0.001 and 0.001; respectively) and increased fibrosis (p = 0.018, 0.02 and 0.013; respectively). The accumulation of mutations per sample in the BCP/PC region is associated with high viral load. Occult hepatitis B infection (OBI) was identified in 5 samples. CONCLUSION: Our results add to the knowledge about HBV genotype-D variants. The accumulation of mutations per sample and OBI seem to play a role in the progression of HBV infection. G1896A was associated with the HBeAg negativity. The preS deletions did not play a role in liver disease progression.

Design and Delivery of Therapeutic siRNAs: Application to MERS-Coronavirus.

BACKGROUND: The MERS-CoV is a novel human coronavirus causing respiratory syndrome since April 2012. The replication of MERS-CoV is mediated by ORF 1ab and viral gene activity can be modulated by RNAi approach. The inhibition of virus replication has been documented in cell culture against multiple viruses by RNAi approach. Currently, very few siRNA against MERS-CoV have been computationally designed and published. METHODS: In this review, we have discussed the computational designing and delivery of potential siRNAs. Potential siRNA can be designed to silence a desired gene by considering many factors like target site, specificity, length and nucleotide content of siRNA, removal of potential off-target sites, toxicity and immunogenic responses. The efficient delivery of siRNAs into targeted cells faces many challenges like enzymatic degradation and quick clearance through renal system. The siRNA can be delivered using transfection, electroporation and viral gene transfer. Currently, siRNAs delivery has been improved by using advanced nanotechnology like lipid nanoparticles, inorganic nanoparticles and polymeric nanoparticles. CONCLUSION: The efficacy of siRNA-based therapeutics has been used not only against many viral diseases but also against non-viral diseases, cancer, dominant genetic disorders, and autoimmune disease. This innovative technology has attracted researchers, academia and pharmaceuticals industries towards designing and development of highly effective and targeted disease therapy. By using this technology, effective and potential siRNAs can be designed, delivered and their efficacy with toxic effects and immunogenic responses can be tested against MERS-CoV.

Legionella saoudiensis sp. nov., isolated from a sewage water sample.

A Gram-stain-negative, bacilli-shaped bacterial strain, LS-1T, was isolated from a sewage water sample collected in Jeddah, Saudi Arabia. The taxonomic position of strain LS-1T was investigated using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences and those of four other genes indicated that strain LS-1T belongs to the genus Legionella in the family Legionellaceae. Regarding the 16S rRNA gene, the most closely related species are Legionella rowbothamii LLAP-6T (98.6 %) and Legionella lytica L2T (98.5 %). The mip gene sequence of strain LS-1T showed 94 % sequence similarity with that of L. lytica L2T and 93 % similarity with that of L. rowbothamii LLAP-6T. Strain LS-1T grew optimally at a temperature of 32 °C on a buffered charcoal yeast extract (BCYE) agar plate in a 5 % CO2 atmosphere and had a flagellum. The combined phylogenetic, phenotypic and genomic sequence data suggest that strain LS-1T represents a novel species of the genus Legionella, for which the name Legionella saoudiensis sp. nov. is proposed. The type strain is LS-1T (=DSM 101682T=CSUR P2101T).