Background and purpose of the studyH. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium.Methods137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined.Results37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 μg/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum.ConclusionsThe most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 μg/ml, respectively.

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Tyrosinase, a widely spread enzyme in micro-organisms, animals, and plants, participates in two rate-limiting steps in melanin formation pathway which is responsible for skin protection against UV lights' harm whose functional deficiency result in serious dermatological diseases. This enzyme seems to be responsible for neuromelanin formation in human brain as well. In plants, the enzyme leads the browning pathway which is commonly observed in injured tissues that is economically very unfavorable. Among different types of tyrosinase, mushroom tyrosinase has the highest homology with the mammalian tyrosinase and the only commercial tyrosinase available. In this study, ligand-based pharmacophore drug discovery method was applied to rapidly identify mushroom tyrosinase enzyme inhibitors using virtual screening. The model pharmacophore of essential interactions was developed and refined studying already experimentally discovered potent inhibitors employing Docking analysis methodology. After pharmacophore virtual screening and binding modes prediction, 14 compounds from ZINC database were identified as potent inhibitors of mushroom tyrosinase which were classified into five groups according to their chemical structures. The inhibition behavior of the discovered compounds was further studied through Classical Molecular Dynamic Simulations and the conformational changes induced by the presence of the studied ligands were discussed and compared to those of the substrate, tyrosine. According to the obtained results, five novel leads are introduced to be further optimized or directly used as potent inhibitors of mushroom tyrosinase.

Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications. RBA was designed according to its reported base pair sequence and secondary structure. The HADDOCK on line docking program was used to predict a suitable RBP4-RBA mode of interaction to start MDs with. MDs methodology was used to analyze the final complex stability and detect interacting residues. Eventually, we conclude that single strand located bases are the key components that conduct the intercalation phenomenon with big targets rather than those involving loops and folded motifs, to encompass targets and probably inhibit their activity. Also, UV-visible, circular dichroism and fluorescence spectroscopy measurements confirmed the interactions between RBA and RBP4 and RBP4-RBA complex formation.

This research is an effort to further understand the physicochemical interaction between the novel drug, mitoxantrone (MTX) and its biologic receptor, DNA. The ultimate goal is to design drugs that interact more with DNA. Understanding the physicochemical properties of the drug as well as the mechanism by which it interacts with DNA, it should ultimately allow the rational design of novel anti-cancer or anti-viral drugs. Molecular modelling on the complex formed between MTX and DNA presented that this complex was indeed fully capable of participating in the formation of a stable intercalation site. Furthermore, the molecular geometries of MTX and the DNA bases (adenine, guanine, cytosine and thymine) were optimized with the aid of the B3LYP/6-31G* method. The properties of the isolated intercalator and its stacking interactions with the adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were studied with the DFTB method (density functional tight-binding), an approximate version of the DFT method, that was extended to cover the London dispersion energy. The B3LYP/6-31G* stabilization energies of the intercalator...base pair complexes were found 10.06 kcal/mol and 21.64 kcal/mol for AT...MTX and GC...MTX, respectively. It was concluded that the dispersion energy and the electrostatic interaction contributed to the stability of the intercalator.DNA base pair complexes. The results concluded from the comparison of the DFTB method and the Hartree-fock method point out that these methods show close results and support each other.

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In this pandemic SARS-CoV-2 crisis, any attempt to contain and eliminate the virus will also stop its spread and consequently decrease the risk of severe illness and death. While ozone treatment has been suggested as an effective disinfection process, no precise mechanism of action has been previously reported. This study aimed to further investigate the effect of ozone treatment on SARS-CoV-2. Therefore, virus collected from nasopharyngeal and oropharyngeal swab and sputum samples from symptomatic patients was exposed to ozone for different exposure times. The virus morphology and structure were monitored and analyzed through Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Atomic Absorption Spectroscopy (AAS), and ATR-FTIR. The obtained results showed that ozone treatment not only unsettles the virus morphology but also alters the virus proteins’ structure and conformation through amino acid disturbance and Zn ion release from the virus non-structural proteins. These results could provide a clearer pathway for virus elimination and therapeutics preparation.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus.Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C-like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 7 April 2020 doi:10.20944/preprints202004.0084.v1 compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.