Ronald Viola
University of Toledo, OH·Chemistry
Fungal infections are among the leading causes of human death, and the danger is growing because many fungi now resist most front-line antifungal drugs and few effective drugs exist against the more aggressive species. About 30% of drugs in clinical use work by covalent modification, forming a permanent chemical bond with their target, yet until recently none were deliberately designed to act that way.
- Fields
Chemistry
Pharmacology
Microbiology & Immunology
- Topics
antifungal drug development
covalent inhibitors
enzyme inactivators
- Grants
- 1 known grant, through May 2028
What they work on
- Optimize the potency and target selectivity of novel covalent inactivators of an essential fungal enzyme in a uniquely microbial pathway, increasing their reactivity once bound to the target.
- Test whether attaching conjugate partners lets these covalent inactivators exploit fungal nutrient uptake systems to reach toxic intracellular levels in Candida species.
- Rank the new agents by fungal growth inhibition and killing assays against both wild-type and drug-resistant Candida strains to assess target selectivity and efficacy.
- Evaluate lead candidates for ADME, pharmacokinetic and toxicity properties, then test efficacy in animal models of systemic (disseminated) and oral fungal infection.
More about the research
The central hypothesis here is that a new class of covalent inactivators, purpose-built to modify a previously untested fungal target, can work against both ordinary and drug-resistant fungi and sidestep existing resistance mechanisms.
Why it matters
Drug-resistant fungal infections, including those caused by Candida, are difficult to treat and especially dangerous for people with weakened immune systems. Compounds that permanently inactivate an essential, uniquely microbial fungal enzyme could become antifungal drugs that work where current ones fail, since they act on a target that existing resistance mechanisms were not built to defend.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Karen Norris
University of Georgia, GA·Microbiology & Immunology
Test whether the NXT-2 vaccine, a lab-made peptide based on a fungal protein shared across species, triggers strong immune responses in nonhuman primates.
Seok-Yong Lee
Duke University, NC·Biophysics
Determine how the echinocandin caspofungin blocks the fungal cell-wall enzyme β-1,3-D-glucan synthase (GS) and how Fks1 mutations cause resistance, using cryo-EM structures, enzyme assays and computational methods.
Micah McClain
Duke University, NC·Medicine & Clinical Research
Track how the blood immune response changes over the course of invasive candidiasis, using bulk RNA-sequencing of serial whole-blood samples from three existing patient biobanks.
The school
University of Toledo: 10 labs on PI Pages, $73M a year on research, 120 research doctorates a year.
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