RESUMO
The search for alternative naturally occurring antimicrobial agents will always continue, especially when emerging diseases like COVID-19 provide an urgency to identify and develop safe and effective ways to prevent or treat these infections. The purpose of this study was to evaluate the potential antimicrobial activity as well as antioxidant properties of commercial samples from four traditional medicinal plants used in Central America: Theobroma cacao, Bourreria huanita, Eriobotrya japonica, and Elettaria cardamomum. Ethanolic extracts were prepared from commercial products derived from the seeds or flowers of these plants. Total phenolics and antioxidant activity were assessed using commercial kits. The cytotoxicity and antiviral activity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) were evaluated using the XTT colorimetric assay and a SARS-CoV-2 delta pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were used to calculate the therapeutic index (TI). Additionally, the antibacterial activity against Escherichia coli and Staphylococcus epidermidis was tested using a spectrophotometric method. The extracts showed total phenolics in the range of 0.06 to 1.85 nM/µL catechin equivalents, with T. cacao bean extract showing the highest content. The antioxidant activity showed values between 0.02 and 0.44 mM Trolox equivalents. T. cacao bean extract showed the highest antioxidant activity. Most plant extracts showed zero to moderate selective antiviral activity; however, one T. cacao beans sample showed excellent antiviral activity against SARS-CoV-2 with a TI value of 30.3, and one sample of E. japonica showed selective antiviral activity with a TI value of 18.7. Significant inhibition of E. coli and S. epidermidis by an E. japonica ethanolic extract (p<0.001) was observed using a spectrophotometric method that monitors bacterial growth over time. Additionally, ethanolic extracts of E. cardamomum showed significant inhibition of S. epidermidis growth (p<0.001). The results warrant further investigation of the antimicrobial and antioxidant properties of these plant extracts.
RESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Several variants of SARS-CoV-2 have emerged worldwide. These variants show different transmissibility infectivity due to mutations in the viral spike (S) glycoprotein that interacts with the human angiotensin-converting enzyme 2 (hACE2) receptor and facilitates viral entry into target cells. Despite the effective SARS-CoV-2 vaccines, we still need to identify selective antivirals, and the S glycoprotein is a key target to neutralize the virus. We hypothesize that small molecules could disrupt the interaction of S glycoprotein with hACE2 and inhibit viral entry. We analyzed the S glycoprotein-hACE2 complex structure (PDB: 7DF4) and created models for different viral variants using visual molecular dynamics (VMD) and molecular operating environment (MOE) programs. Moreover, we started the hits search by performing structure-based molecular docking virtual screening of commercially available small molecules against S glycoprotein models using OEDocking FRED-4.0.0.0 software. The FRED-4.0.0.0 Chemguass4 scoring function was used to rank the small molecules based on their affinities. The best candidate compounds were purchased and tested using a standard SARS-CoV-2 pseudotyped cell-based bioassay to investigate their antiviral activity. Three of these compounds, alone or in combination, showed antiviral selectivity. These small molecules may lead to an effective antiviral treatment or serve as probes to better understand the biology of SARS-CoV-2.