Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response Box®: In Vitro and In Silico Analyses

Mariana Ingrid Dutra da Silva Xisto; Rodrigo Rollin-Pinheiro; Yuri de Castro-Almeida; Giulia Maria Pires Dos Santos-Freitas; Victor Pereira Rochetti; Luana Pereira Borba-Santos; Yasmin da Silva Fontes; Antonio Ferreira-Pereira; Sonia Rozental; Eliana Barreto-Bergter

doi:10.3390/jof9020187

Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response Box^®: In Vitro and In Silico Analyses

J Fungi (Basel). 2023 Jan 31;9(2):187. doi: 10.3390/jof9020187.

Affiliations

¹ Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
² Laboratório de Biologia Celular de Fungos, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
³ Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Abstract

Mucormycosis is considered concerning invasive fungal infections due to its high mortality rates, difficult diagnosis and limited treatment approaches. Mucorales species are highly resistant to many antifungal agents and the search for alternatives is an urgent need. In the present study, a library with 400 compounds called the Pandemic Response Box^® was used and four compounds were identified: alexidine and three non-commercial molecules. These compounds showed anti-biofilm activity, as well as alterations in fungal morphology and cell wall and plasma membrane structure. They also induced oxidative stress and mitochondrial membrane depolarization. In silico analysis revealed promising pharmacological parameters. These results suggest that these four compounds are potent candidates to be considered in future studies for the development of new approaches to treat mucormycosis.

Keywords: Pandemic Response Box®; Rhizopus; antifungal agents; biofilm; in silico analyses.

Grants and funding

This study was supported by the following Brazilian funding agencies: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, https://www.gov.br/capes/pt-br), which supported Rochetti, V.P., Borba-Santos, L.P. and Fontes, Y. S.; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, https://www.gov.br/cnpq/pt-br), which supported Castro-Almeida, Y., Ferreira-Pereira, A., Rozental, S. and Barreto-Bergter, E.; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, https://www.faperj.br/) (Rede Micologia, RJ), which supported Rollin-Pinheiro, R., Xisto, M.I.D.S., Borba-Santos, L.P., Ferreira-Pereira, A., Rozental, S. and Barreto-Bergter, E. Xisto, M.I.D.S. was also supported by FAPERJ #E-26/202.051/2020 and Rollin-Pinheiro, R. was also supported by FAPERJ #E-26/200.591/2022 and #E-26/210.355/2022. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding support was provided to buy reagents for the development of the study.