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Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine

New publication from Heze-Sapience International.

Abstract:

Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are −5.8 and −5.4 kcal mol-1 respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase.

Download link: https://www.frontiersin.org/articles/10.3389/fbinf.2023.1123307/pdf

In Silico Evaluation of the Antioxidant, Anti-Inflammatory, and Dermatocosmetic Activities of Phytoconstituents in Licorice (Glycyrrhiza glabra L.)

The global demand for herbal cosmetics is vastly increasing due to their health benefits and relative safety. Glycyrrhiza spp. extracts are used in cosmetic preparations due to their skin-whitening, antisensitizing, and anti-inflammatory properties. The aim of this work is to computationally evaluate the bioactive constituents of licorice (Glycyrrhiza glabra L.) that possess antioxidant, anti-inflammatory, and dermatocosmetic activities, and elucidate the dynamics of their molecular targets. The used methods are skin permeability prediction, target prediction, molecular docking, and molecular dynamic simulation (MDS). The results show that, at a skin permeation cut-off value of −6.0 cm/s, nine phytoconstituents of licorice (furfuraldehyde, glucoliquiritin apioside, glycyrrhizin, isoliquiritin, licopyranocoumarin, licuraside, liquiritigenin, liquiritin, and liquiritin apioside) were workable. Molecular target prediction results indicate probability for tyrosinase, 11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1), monoamine oxidase B, steroid 5-alpha-reductase 1, and cyclo-oxygenase-1. On the basis of molecular docking, glucoliquiritin apioside and glycyrrhizin had the best antioxidant, anti-inflammation, and dermatocosmetic activities. MDS results show that the complexes had good stability, and MMGBSA results indicate that the complexes had satisfactory binding energy. Overall, this study demonstrates that licorice extracts are potential antioxidants that could enhance histological dermal and epidermal properties, and reduce the level of inflammatory and wrinkling markers.

Download link: https://www.mdpi.com/2079-9284/10/3/69/pdf