Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

The incidence of infections by non-albicans Candida species, including Candida krusei, is increasing. Candida krusei exhibits intrinsic resistance to fluconazole and rapidly develops acquired resistance to other antifungals. Moreover, this yeast can form biofilm with increased resistance. Hence, there is a need to develop novel therapeutic strategies to combat infections caused by this pathogen. One such approach is through combination therapy with natural compounds, such as polyunsaturated fatty acids (PUFAs). This study aims to investigate the effect of PUFAs on fluconazole susceptibility of C. krusei biofilms, as well as the conserved nature of these effects in the Caenorhabditis elegans infection model. C. krusei biofilms were exposed to various fatty acids as well as combinations of fluconazole and linoleic acid (LA) or gamma-linolenic acid (GLA). The effect of these treatments on biofilm formation, cell ultrastructure, membrane integrity, oxidative stress and efflux pump activity was evaluated. In addition, the ability of the PUFAs to prolong survival and reduce the fungal burden of infected C. elegans, in the absence and presence of fluconazole, was assessed. Two PUFAs, LA and GLA had displayed significant inhibition of C. krusei biofilms and both of them increased the susceptibility of C. krusei biofilm to fluconazole in vitro via induction of oxidative stress, cell membrane damage, and disruption of efflux pump activity. These PUFAs also extended the lifespan of infected nematodes and displayed a potentiating effect with fluconazole in this model. This may pave the way for future studies into novel antifungal drug targets and treatment options. The pathogenic yeast, Candida krusei, is naturally resistant to the antifungal drug, fluconazole. This study finds that polyunsaturated fatty acids, linoleic and gamma-linolenic acid, can inhibit C. krusei and overcome this resistance of in vitro biofilms, as well as in a nematode infection model.

The novel β-coronavirus, SARS-CoV-2, responsible for the coronavirus disease 2019 (COVID-19) emerged in China in December 2019. Due to its high transmission and infection rate, it has spread around the world and has transformed into a ravaging global pandemic with enormously unprecedented impacts globally on human, social, and economic health. Just like SARS-CoV and MERS-CoV, there is no specific antiviral drug for its treatment. The only available therapeutics are supportive and symptom-based. Thus, scientists are harnessing various strategies to expedite drug development. One such approach is drug repurposing through computational screening of phytocompounds, which leverages proteins that are essential for the entry, replication, pathogenesis, assembly, and release of SARS-CoV-2. Here, we review the available literature on molecular docking of phytoligands against SARS-CoV-2 integral proteins, in a bid to update our current knowledge and identify the most promising molecules. The overwhelming majority of the promising lead compounds are either phenolics or terpenoids. Furthermore, of the elucidated SARS-CoV-2 targets, the main protease (3CL^pro) appears as one of the most attractive druggable targets. Notably, compounds such as rutin, quercetin, luteolin, neoandrographolide, curcumin, and others with evident anti-inflammatory benefits, in addition to their predicted anti-SARS-CoV-2 properties, deserve further studies to validate their activity.

The emergence of multidrug-resistant Neisseria gonorrhoeae has intensified the need for innovative therapeutic strategies. One promising but underexplored target is the Hfq protein, a key regulator in bacterial stress response and pathogenesis. In this study, we employed a computer-aided drug discovery approach to screen phytochemicals from traditionally used anti-gonorrheal plants for their potential to inhibit Hfq. Molecular docking identified several compounds, including Hellebrigenin 3-acetate, Carpaine, β-amyrin, α-amyrin, Rosarin, Oleanolic acid, and Epigallocatechin 3-O-gallate, with binding affinities surpassing that of the reference drug, Ceftriaxone. Molecular dynamics simulations revealed that Carpaine and Oleanolic acid formed the most stable Hfq complexes, exhibiting low RMSD values (0.73 nm and 0.66 nm) and compact Rg profiles (~ 1.4 nm), indicating strong structural stabilization. ADMET analysis suggested moderate intestinal absorption and oral bioavailability, though some compounds showed risks of liver toxicity and CYP2D6 inhibition. Carpaine demonstrated the most favorable binding free energy and prolonged systemic retention, making it an up-and-coming lead candidate. Importantly, evolutionary analysis confirmed the conservation of the Hfq active site, further supporting its viability as a therapeutic target. These findings reveal the potential of plant-derived compounds, particularly Carpaine and Oleanolic acid, as novel Hfq inhibitors, providing a strong foundation for future experimental validation and the development of alternative therapies against multidrug-resistant N. gonorrhoeae.