Trichomoniasis is the most prevalent non-viral sexually transmitted infection worldwide. It has been estimated that 276 million new infections occurred in 2008 with 11.5% increase over the 2005 incidence rate [1]. Worldwide, the estimated prevalence rates vary with geographic location, age, race, community and the method used for diagnosis. In 2016, the WHO global estimate for trichomoniasis in women was estimated at 5.3% and 0.6% in men with a total incidence of 156 million cases [2]. In Egypt, a prevalence rate of 8.0% was recently documented among symptomatic women in Beni Suef Governorate [3] ; in addition to 11% in Benha, Qalyubia Governorate [4] , and 5% in Cairo [5]. Another older study recorded prevalence rate of 27-57% using different techniques for diagnosing trichomoniasis in Shebin El-Kom, Menoufia Governorate [6]. While infections are mostly asymptomatic in men, women usually present with vaginal discharge, pruritus and dysuria [7,8]. Trichomoniasis is considered an important risk factor for herpes simplex virus type II infections and HIV transmission and acquisition [9,10]. Data from studies in Africa recorded an increase in HIV transmission associated with trichomoniasis [11-13]. In an American study, the investigators detected T. vaginalis in 20% of HIV-infected pregnant women using PCR assay [14]. Moreover, it may be associated with cervical cytological abnormalities and cervical cancer [15-18]. Such a difference in clinical traits as virulence, pathogenicity and drug resistance, signifies the need to link phenotypic variation to genotype [19]. In Egypt, former attempts to investigate the diversity of T. vaginalis included isoenzyme patterns [20] , serotyping [21] , immunoblotting [22,23] , biological variability [24,25] and HSP70-RFLP [26]. These studies concluded that the different clinical isolates have different and common patterns at the levels of antigens, immunogens, pathogenicity and MTZ resistance. Molecular typing methods revealed a two-type population structure for T. vaginalis, type I and type II [27-31]. Genotype I infections were found to have lower probability of associated discolored discharge, especially bloody discharge, bleeding during physical examination, or presence of greater than 20% clue cells. Infections with genotype II were significantly associated with these pathological findings. The increase in clue cells seen with genotype II are indicative of bacterial vaginosis, providing a change in the vaginal microenvironment that is favorable for infection with other microbial pathogens. Genetic diversity for T.
Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies.
In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2-Thioxoimidazolidin-4-one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum-sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes. K E Y W O R D S2-thioxoimidazolidin-4-one, imidazolidine-2,4-dione, Pseudomonas aeruginosa, quorum sensing, virulence inhibition
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