The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities. We used pseudotyped HIV-1 with the D614G SARS-CoV-2 spike glycoprotein to test its ability to infect ACE2-expressing HEK 293T cells in the presence of diverse natural products, including 21 plant extracts, 7 essential oils, and 13 compounds from plants and fungi. The 50% cytotoxic concentration (CC₅₀) was evaluated using the resazurin method. From these analyses, we determined the inhibitory activity of the extract of Stachytarpheta cayennensis, which had a half-maximal inhibitory concentration (IC₅₀) of 91.65 µg/mL, a CC₅₀ of 693.5 µg/mL, and a selectivity index (SI) of 7.57, indicating its potential use as an inhibitor of SARS-CoV-2 entry. Moreover, our work indicates the usefulness of the pseudotyped-virus system in the screening of SARS-CoV-2 entry inhibitors.

The biofilm is a conglomerate of cells surrounded by an extracellular matrix, which contributes to the persistence of infections. The difficulty in removing the biofilm drives the research for new therapeutic options. In this work, the effect of terpenes (−)-trans-Caryophyllene, (S)-cis-Verbenol, (S)-(−)-Limonene, (R)-(+)-Limonene, and Linalool was evaluated, individually and in combinations on bacterial growth, by assay with resazurin; the formation of biofilm, by assay with violet crystal; and the expression of associated genes, by real-time PCR, in two clinical isolates of Staphyloccocus aureus, ST30-t019 and ST5-t311, responsible for more than 90% of pediatric infections by this pathogen in Paraguay. All combinations of terpenes can inhibit biofilm formation in more than 50% without affecting bacterial growth. The most effective combination was (−)-trans-Caryophyllene and Linalool at a 500 μg/mL concentration for each, with an inhibition percentage of 88%. This combination decreased the expression levels of the sdrD, spa, agr, and hld genes associated with the initial cell adhesion stage and quorum sensing. At the same time, it increased the expression levels of the cap5B and cap5C genes related to the production of capsular polysaccharides. The combinations of compounds tested are promising alternatives to inhibit biofilm formation in S. aureus.

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.