Evidence map›Paper›PMID 35471056›Full record

ArticleMicrobiology spectrum2022

Screening of the Pandemic Response Box Reveals an Association between Antifungal Effects of MMV1593537 and the Cell Wall of

Haroldo C de Oliveira, Rafael F Castelli, Flavia C G Reis, Kirandeep Samby, Joshua D Nosanchuk, Lysangela R Alves, Marcio L Rodrigues

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Cellular and molecular responses ofMicrobiology spectrum · 2026
    Article
  2. Review
  3. Antimicrobial potential of compounds from the MMV pandemic response box and COVID box against carbapenem-resistant Acinetobacter baumannii.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Antifungal Effect of Vitamin DJournal of fungi (Basel, Switzerland) · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Candida auris, a singular emergent pathogenic yeast: its resistance and new therapeutic alternatives.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022
    Review
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Haroldo C de OliveiraInstituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
Rafael F CastelliInstituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
Flavia C G ReisInstituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
Kirandeep SambyMedicines for Malaria Venturegrid.452605.0, Geneva, Switzerland.
Joshua D NosanchukDepartment of Microbiology and Immunology and Division of Infectious Diseases, Albert Einstein College of Medicine of Yeshiva University, New York, New York, USA.
Lysangela R AlvesInstituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.ORCID 0000-0002-1972-2658
Marcio L RodriguesInstituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.ORCID 0000-0002-6081-3439
Fundação Oswaldo Cruz · BRAlbert Einstein College of Medicine · USMedicines for Malaria Venture · CHUniversidade Federal do Rio de Janeiro · BR

Funding

Candida auris extracellular vesicles subvert host immune responsesR21AI156104 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI NOSANCHUK, JOSHUA D · 2021 to 2022
$462k
NIAID NIH HHS R21 AI156104
6 · The paper itself

Abstract

There is an urgent unmet need for novel antifungals. In this study, we searched for novel antifungal activities in the Pandemic Response Box, a collection of 400 structurally diverse compounds in various phases of drug discovery. We identified five molecules which could control the growth of Cryptococcus neoformans, Cryptococcus deuterogattii, and the emerging global threat Candida auris. After eliminating compounds which demonstrated paradoxical antifungal effects or toxicity to mammalian macrophages, we selected compound MMV1593537 as a nontoxic, fungicidal molecule for further characterization of antifungal activity. Scanning electron microscopy revealed that MMV1593537 affected cellular division in all three pathogens. In Cryptococcus, MMV1593537 caused a reduction in capsular dimensions. Treatment with MMV1593537 resulted in increased detection of cell wall chitooligomers in these three species. Since chitooligomers are products of the enzymatic hydrolysis of chitin, we investigated whether surface chitinase activity was altered in response to MMV1593537 exposure. We observed peaks of enzyme activity in C. neoformans and C. deuterogattii in response to MMV1593537. We did not detect any surface chitinase activity in C. auris. Our results suggest that MMV1593537 is a promising, nontoxic fungicide whose mechanism of action, at least in Cryptococcus spp, requires chitinase-mediated hydrolysis of chitin.

Indexed as

Antifungal AgentsCandida aurisChitinasesCryptococcus gattiiCryptococcus neoformansAnimalsCell WallChitinMacrophagesMicrobial Sensitivity TestsAntifungal AgentsChitinChitinasesantifungalsCandida aurisCryptococcusdrug screening

Identifiers

PMID35471056
PMCPMC9241760
OpenAlexW4224855950

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.