Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

Blocking the entry of an HIV-1 targeting CCR5 coreceptor has emerged as an attractive strategy to develop HIV therapeutics. Maraviroc is the only CCR5 antagonist approved by FDA; however, serious side effects limited its clinical use. Herein, 21 novel tropane derivatives (6–26) were designed and synthesized based on the CCR5-maraviroc complex structure. Among them, compounds 25 and 26 had comparable activity to maraviroc and presented more potent inhibitory activity against a series of HIV-1 strains. In addition, compound 26 exhibited synergistic or additive antiviral effects in combination with other antiretroviral agents. Compared to maraviroc, both 25 and 26 displayed higher C max and AUC0–∞ and improved oral bioavailability in SD rats. In addition, compounds 25 and 26 showed no significant CYP450 inhibition and showed a novel binding mode with CCR5 different from that of maraviroc-CCR5. In summary, compounds 25 and 26 are promising drug candidates for the treatment of HIV-1 infection.

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