Protease inhibitors from Theobroma cacao impair SARS-CoV-2 replication in vitro.

SARS-CoV-2 is a newly emerging virus from the Coronaviridae family that has already infected over 700 million people worldwide and killed over 6 million. This virus uses protease molecules to replicate and infect the host, which makes these molecules targets for therapeutic substances to eliminate the virus and treat infected people. Through the protein-protein molecular docking approach, we detected two cystatins from Theobroma cacao, TcCYS3 and TcCYS4, described as papain-like protease inhibitors. These inhibitors decreased SARS-CoV-2 genomic copies without toxicity to Vero cells. There is a need to perform comprehensive studies in relevant animal models and to investigate the action mechanisms of protease inhibitors from Theobroma cacao that control the replication of SARS-CoV-2 in human cells.

Inhibition of extracellular traps by spores of Trichoderma stromaticum on neutrophils obtained from human peripheral blood.

Although the genus Trichoderma is widely used as a biocontrol agent in crops, little is known about its potential impact on the human immune system. In mice, our group has shown that exposition to T. asperelloides spores lead to reduced neutrophil counts in the peripheral blood and in the peritoneal cavity. In addition, T. stromaticum spores produced an inflammatory infiltrate on mice lungs, reducing the levels of IFN-γ and IL-10 cytokines, reactive oxygen species, and receptors of microbial patterns. Here we demonstrate that the interaction of human peripheral neutrophils with T. stromaticum spores also leads to a reduced release of neutrophil extracellular traps (NETs) after induction with the NET-inducer agent phorbol 12-myristate 13-acetate. This interaction also reduced the expression levels of multiple microRNAs, such as miR-221, miR-222, miR-223 and miR-27a, as well as genes related to NETs, such as ELANE, MPO and PADI4. Furthermore, T. stromaticum spores affected the expression of the genes SOCS3, TLR4, CSNK2A1, GSDMD, and NFFKBIA, related to the activation of inflammatory immune responses in neutrophils. Overall, our results suggest T. stromaticum as a potential NET inhibitor and as an immunomodulatory agent. Since this fungus is used as biocontrol in crops, our findings point to the importance of advancing our knowledge on the effects of this bioagent on the human immune system. Finally, the study of the active compounds produced by the fungus is also important for the prospection of new drugs that could be used to block the exacerbation of inflammatory immune responses present in several human diseases.