Taming the SARS-CoV-2-mediated proinflammatory response with BromAc®
Geovane Marques Ferreira, Felipe Alves Clarindo, Ágata Lopes Ribeiro, Letícia Gomes-De-Pontes, Luciana Debortoli De Carvalho, Olindo Assis Martins-Filho, Flávio Guimarães Da Fonseca, Mauro Martins Teixeira, Adriano De Paula Sabino, Mathew Suji Eapen, David L Morris, Sarah J Valle, Jordana Grazziela Alves Coelho-Dos-Reis
Frontiers in Immunology, doi:10.3389/fimmu.2023.1308477
Introduction: In the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated. Methods: An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed. Results and discussion: BromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc® may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc® on leukocytes upon viral stimuli showed that BromAc® was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc® treatment increased steady-state HLA-DR expression in CD14 + monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc® treatment. Additionally, BromAc® downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups Frontiers in Immunology frontiersin.org 01
Ethics statement The studies involving humans were approved by Ethics Committee of Universidade Estadual de Santa Cruz (UESC) and Federal University of Minas Gerais (UFMG). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.
Author contributions
Funding The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Fundacão de Amparo à Pesquisa de Minas Gerais (FAPEMIG, APQ-01499-21), Conselho Nacional de Desenvolvimento Cientıfco e Tecnoloǵico (CNPq MCTI/CNPQ/Universal), EMBRAPII (Process # 30275) and Coordenacão de Aperfeicoamento de Pessoal de Nıvel Superior (CAPES). FF, OM, MT, and JC-d-R received PQ fellowships from CNPq. This work was also funded by extramural resources from Mucpharm Pty Ltd (AU). OF participated in the fellow program supported by the Universidade do Estado do Amazonas (PROVISIT N°005/2023-PROPESP/UEA).
Conflict of interest SV and DM are shareholders of Mucpharm Pty Ltd. and provided scientific input on the protocol and design of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Mucpharm Pty Ltd. The funder had the following..
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