Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

58-POS Board 19 ANTIVIRAL AND VIRUCIDAL EFFECT OF CHALCONE AND KAEMPFEROL DERIVATIVES AGAINST HRSV INFECTION IN HEP 2 CELL CULTURE Jefferson de Souza 1 ; Igor da Silva Salvioni 1 ; Jessica Maróstica de Sa 1 ; Alvaro Luiz Helena 2 ; Thaina da Silva Rodrigues 1 ; Luis Octavio Regasini 2 ; Ícaro Putinhon Caruso 1 ; Marcelo Andres Fossey 1 ; Mark E Peeples 3 ; Fatima Pereira de Souza 1 ; 1 UNESP, Department of Physics and Multiuser Center of Biomolecular Innovation, Institute of Biosciences, Letters and Exact Sciences, São José do Rio Preto, Brazil 2 UNESP, Deparment of Chemistry , Institute of Biosciences, Letters and Exact Sciences, São José do Rio Preto, Brazil 3 Abigail Wexner Research Institute at Nationwide Children's Hospital, Center for Vaccines and Immunity, Columbus, OH, USA Human respiratory syncytial virus (hRSV) is the most common pathogen responsible for lower respiratory diseases in children, causing bronchiolitis and pneumonia, and associated with significant morbidity and mortality. Nearly all children by two years of age have been infected with hRSV, with ~2% requiring hospitalization. There is currently no approved vaccine for this age group and no approved antiviral drugs. Safe therapies are needed. Natural compounds, such as kaempferol and chalcone, have shown potential benefits against other viruses, inhibiting the viral cycle by several pathways. The objective of this work was to investigate the effect of chalcone, kaempferol and their derivates on RSV infection of cultured cells. HEp-2 cells were inoculated with an MOI of 0.2 for 72 hours. The inoculum was fresh culture medium containing non-cytotoxic concentrations of the tested molecules. A second test was to pretreat the cells with the compounds before infection. A third test was for direct virucidal activity, adding different concentrations to a viral solution and incubating for 2 hours at 37C before inoculating the cells, then replacing the inoculum with fresh medium. These test examine different phases of the RSV cycle, adhesion, internalization, replication and budding. The results showed that of the forty molecules, six were effective post inoculation, one of them effective for pretreatment as well, at the rate of 62% to 13% of cellular protection. Five of the molecules were virucidal, to 51% to 12%. These results suggest that the molecules might block the interaction site on a cell receptor for the F or G proteins of RSV, preventing the virus from fusing with the host cell membrane, or interact with the M, M2-1/2, P, N or L proteins involved in viral replication and assembly, delaying the infection process and the formation of new infectious virus particles. These compounds warrant further analysis for prophylaxis and therapy against RSV infection. Financial support: FAPESP: 2021/14349-1, 2022/01492-3, 2023/00483-3, CNPQ and FINEP.

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