In Silico and In Vitro Studies of Terpenes from the Fabaceae Family Using the Phenotypic Screening Model against the SARS-CoV-2 Virus.

In 2019, the emergence of the seventh known coronavirus to cause severe illness in humans triggered a global effort towards the development of new drugs and vaccines for the SARS-CoV-2 virus. These efforts are still ongoing in 2024, including the present work where we conducted a ligand-based virtual screening of terpenes with potential anti-SARS-CoV-2 activity. We constructed a Quantitative Structure-Activity Relationship (QSAR) model from compounds with known activity against SARS-CoV-2 with a model accuracy of 0.71. We utilized this model to predict the activity of a series of 217 terpenes isolated from the Fabaceae family. Four compounds, predominantly triterpenoids from the lupane series, were subjected to an in vitro phenotypic screening in Vero CCL-81 cells to assess their inhibitory activity against SARS-CoV-2. The compounds which showed high rates of SARS-CoV-2 inhibition along with substantial cell viability underwent molecular docking at the SARS-CoV-2 main protease, papain-like protease, spike protein and RNA-dependent RNA polymerase. Overall, virtual screening through our QSAR model successfully identified compounds with the highest probability of activity, as validated using the in vitro study. This confirms the potential of the identified triterpenoids as promising candidates for anti-SARS-CoV-2 therapeutics.

A potential antiviral against COVID-19 obtained from Byrsonima coccolobifolia leaves extract.

In this study, we specifically focused on the crude methanolic leaf extract of Byrsonima coccolobifolia, investigating its antifungal potential against human pathogenic fungi and its antiviral activity against COVID-19. Through the use of high-performance liquid chromatography coupled with electrospray ionization ion trap tandem mass spectrometry, direct infusion electrospray ionization ion trap tandem mass spectrometry, and chromatographic dereplication procedures, we identified galloyl quinic acid derivatives, catechin derivatives, proanthocyanidins, and flavonoid glycosides. The broth dilution assay revealed that the methanolic leaf extract of B. coccolobifolia exhibits antifungal activity against Cryptococcus neoformans (IC50 = 4 µg/mL). Additionally, docking studies were conducted to elucidate the interactions between the identified compounds and the central residues at the binding site of biological targets associated with COVID-19. Furthermore, the extract demonstrated an in vitro half-maximum effective concentration (EC50 = 7 µg/mL) and exhibited significant selectivity (>90%) toward SARS-CoV-2.

The translational challenge in Chagas disease drug development

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.