Abdo A. Elfiky

Postmenopausal osteoporosis is a common disorder accompanied with estrogen deficiency in women. Plants containing phytoestrogens and amino acids have been used in the osteoporosis treatment. The present study aims to evaluate the estrogen-like activity of the Cicer arietinum extract (CAE) and its ability to inhibit osteoclastogenesis process. These achieved by investigating the binding of its active phytoestrogens (genistein, daidzein, formononetin and biochanin A) to the estrogen receptors (ER) α and β of rats and human in silico. In addition, in vivo study on ovariectomized (OVX) rats is performed. For in vivo study, twenty four rats were divided into four groups (n= 6). Group I is the sham control rats which administered distilled water. Groups II, III, and IV are OVX groups which administered distilled water, CAE (500 mg/kg), and alendronate; respectively. The docking study revealed that the phytoestrogens docked into the protein active site with binding energies comparable with that of estrogens (estriol and β-estradiol) which means the similarity between the estrogenic contents of CAE and the ensogenous ones. Additionally, in vivo study revealed that CAE reverse TRAP5b and RANKL levels that drastically increased in the untreated OVX group. But, it trigger upregulation of OPG, enhance the OPG/RANKL ratio and modulate the bone and uterus alterations of OVX group. Phytoestrogens and the bone-protective amino acids contents of CAE could be responsible for their estrogen-like effect and antiosteoporotic activity. These results concluded that CAE is an attractive candidate for developing a potential therapeutic cheap agent used as an alternative to the synthetic estrogen replacement therapy. Further, in vivo validation is required for its clinical application. © 2018 by the C.M.B. Association.

Background: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro). Objective: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti-COVID-19 treatment, this study lays the groundwork for further experimental research to investi-gate these compounds' efficacy and potential medical uses to treat COVID-19. Methods: New heterocyclic compounds were synthesized through the first reaction of cyclohexane-1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds. Results: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules. Conclusion: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib. © 2023 Bentham Science Publishers.

Aim: Mucormycosis (zygomycosis) is a rare fungal infection that affects humans (40-100% mortality). Rhizopus oryzae is the primary fungus responsible for 70% of mucormycosis cases. RNA-dependent RNA polymerase (RdRp) is a vital enzyme accountable for the RNA polymerization process in different organisms, including R. oryzae. Blocking this enzyme has been previously reported as a successful strategy to eradicate viral infections. Materials & methods: AutoDock Vina is utilized for the calculation of binding affinities of Sofosbuvir, Ribavirin and uridine triphosphate nucleotide to the fungal RdRp model built by homology modeling (no solved structures available). Results: Sofosbuvir shows excellent binding affinity to the fungal RdRp in silico. Conclusion: In this study, R. oryzae RdRp is suggested to be a possible protein target against the nucleotide inhibitor, Sofosbuvir. © 2019 Future Medicine Ltd.

Objectives: Mucormycosis has been reported associated with SARS-CoV-2 infections during the last year. The viral RNA-dependent RNA polymerase (RdRp) was proved to be a critical protein target in viral and fungal pathogens. The human inosine monophosphate dehydrogenase (IMPDH) is an evolved antiviral and antimicrobial therapeutic target. The aim is to triple-hit the viral and fungal RdRps and the human IMPDH. Methods: In the current study, molecular docking combined with molecular dynamics simulation (MDS) is utilized to test nucleotide inhibitors against the RdRps of SARS-CoV-2 and Rhizopus oryzae (the main causing agent of mucormycosis) RdRp. Additionally, the same inhibitors targeted the human Inosine monophosphate dehydrogenase (IMPDH). Results: The results reveal a comparable binding affinity of four nucleotide derivatives compared to remdesivir and sofosbuvir against both IMPDH and the RdRps of SARS-CoV-2 and Rhizopus oryzae. The binding affinities are calculated using different conformations of the RdRps after 100 ns MDS and trajectories clustering. Conclusions: The current study suggests the triple inhibition potential of four nucleotide inhibitors against SARS-CoV-2 & R. oryzae RdRps and the human IMPDH, while experimental validation is yet to be performed. © 2023