SARS-Cov-2 Omicron variant and its highly transmissible sublineages amidst news of emerging hybrid variants strengthen the evidence of its ability to rapidly spread and evolve giving rise to ...unprecedented future waves. Owing to the presence of isolated RBD, monomeric and trimeric Cryo-EM structures of spike protein in complex with ACE2 receptor, comparative analysis of Alpha, Beta, Gamma, Delta, and Omicron assist in a rational assessment of their probability to evolve as new or hybrid variants in future. This study proposes the role of hydration forces in mediating Omicron function and dynamics based on a stronger interplay between protein and solvent with each Covid wave. Mutations of multiple hydrophobic residues into hydrophilic residues underwent concerted interactions with water leading to variations in charge distribution in Delta and Omicron during molecular dynamics simulations. Moreover, comparative analysis of interacting moieties characterized a large number of mutations lying at RBD into constrained, homologous and low-affinity groups referred to as mutational drivers inferring that the probability of future mutations relies on their function. Furthermore, the computational findings reveal a significant difference in angular distances among variants of concern due 3 amino acid insertion (EPE) in Omicron variant that not only facilitates tight domain organization but also seems requisite for characterization of mutational processes. The outcome of this work signifies the possible relation between hydration forces, their impact on conformation and binding affinities, and viral fitness that will significantly aid in understanding dynamics of drug targets for Covid-19 countermeasures. The emerging scenario is that hydration forces and hydrophobic interactions are crucial variables to probe in mutational analysis to explore conformational landscape of macromolecules and reveal the molecular origins of protein behaviors.
L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, ...proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm
to 5000 cm
respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.
A public health concern emerging from a zoonotic disease. Monkeypox is caused by the orthopoxvirus specie Monkeypox virus (MPXV). Monkeypox was identified as the most common orthopoxvirus infection ...in humans following the eradication of smallpox. Monkeypox has a similar clinical presentation to smallpox. The MPXV is now considered a high-threat pathogen that causes a serious public-health problem. The continuous spread of Monkeypox virus from West Africa to all other places around the world throughout 2018 to 2022, have raised concerns that MPXV could have emerged to acquire the immunological and ecological niche vacated by smallpox virus. This review highlights the current knowledge about Monkeypox evolution, infection biology, and epidemiology around the world since from 1970 to 2022, with a focus on the human, viral, and cellular factors that influence virus emergence, infection, spread, and maintenance in nature. This paper also discusses the current therapeutic options for Monkeypox treatment and control. Under the right conditions, with limited smallpox vaccination and very little orthopoxvirus immunity in some areas of the world, MPXV could become a more efficient human pathogen. Finally, the review identified knowledge gaps, particularly in terms of identifying a definitive reservoir host for monkeypox and proposes future research endeavors to address the unanswered questions.
Pathogenesis of Oncoviruses: A Systemic Review Abedien, Zain Ul; Gul, Kainat; Khan, Sara ...
Han'gug mi'saengmul saengmyeong gong haghoeji/Han-guk misaengmul saengmyeong gonghak hoeji,
06/2023, Letnik:
51, Številka:
2
Journal Article
Odprti dostop
Viral oncology is focused on understanding the relationship between cancer and viruses, which are known to play a role in the development of certain types of cancer. Approximately 15-20% of human ...cancers are believed to be caused by oncogenic viruses, and as a result, there is significant interest in understanding how these viruses contribute to cancer development. There are several viruses that have been linked to cancer, including human papillomavirus, hepatitis B and C virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. Each of these viruses is associated with different types of cancer, and the mechanisms by which they contribute to cancer development are diverse. This article discusses these mechanisms as well as current and future strategies for preventing and treating virus-associated cancers with the goal of presenting a thorough review of the current state of knowledge in viral oncology and to highlight the importance of continued research in this field. KCI Citation Count: 0
Roxadustat, a small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase domain 2 (HIF-PHD2) has been recently overruled by the American Food and Drug Administration (FDA) in Phase 3 ...clinical trials. This study provides insights into the dynamics of Roxadustat with PHD2 and proposes two FDA-approved drugs; Pemetrexed and Valrubicin to treat chronic kidney disease (CKD). Role of chemical scaffolds such as synthetic pyrimidine-based antifolate is found critical for PHD2 inhibitory activity, which is concurrent with the experimental findings for stimulating Endogenous erythropoietin (EPO) gene expression. Furthermore, Fe+2 and Mn+2 in solution are essential for imparting structural stability to the screened carboxylic and non-carboxylic acid drugs. Comparative analysis of FDA-approved drugs namely, Roxadustat, two-hit carboxylic, and non-carboxylic-acid type compounds (Pemetrexed and Valrubicin), as well as the control ligands (KU1 and 4JR), unveil structural dynamics of Roxadustat and its failure. However, the proposed FDA compounds, Pemetrexed and Valrubicin, used to treat mesothelioma, non-small cell lung cancer, and bladder cancer should be subjected to in vitro analysis for renal anemia.
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•Roxadustat toxic trait is both experimental and computational.•Pemetrexed, an FDA-approved drug is screened as a potential PHD2 inhibitor.•Fe+2 and Mn+2 are directly involved in stabilization of metal center active site.•ASP 218 is essential for metal ions to maintain their coordination geometries.
Viral oncology is focused on understanding the relationship between cancer and viruses, which are known to play a role in the development of certain types of cancer. Approximately 15-20% of human ...cancers are believed to be caused by oncogenic viruses, and as a result, there is significant interest in understanding how these viruses contribute to cancer development. There are several viruses that have been linked to cancer, including human papillomavirus, hepatitis B and C virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. Each of these viruses is associated with different types of cancer, and the mechanisms by which they contribute to cancer development are diverse. This article discusses these mechanisms as well as current and future strategies for preventing and treating virus-associated cancers with the goal of presenting a thorough review of the current state of knowledge in viral oncology and to highlight the importance of continued research in this field.
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