Predicting the Anti-SARS-CoV-2 Potential of Isoquinoline Alkaloids from Brazilian Siparunaceae Species Using Chemometric Tools

The COVID-19 pandemic has caused over 7 million deaths globally in the past four years. Siparuna spp. (Siparunaceae), which is used in Brazilian folk medicine, is considered a genus with potential antiviral alternatives. This study explored the correlation between phytochemicals in Siparuna leaf extracts ( S. ficoides , S. decipiens , S. glycycarpa , S. reginae , and S. cymosa ) and their potential against various SARS-CoV-2 targets. In vitro assays examined interactions between the spike protein and the ACE2 receptor, protease activity, and viral replication inhibition in Calu-3 cell models. UHPLC-MS/MS analysis, processed with MZmine and evaluated chemometrically, revealed isoquinoline alkaloids with bulbocapnine, showing promising therapeutic potential. Predictions regarding absorption, distribution, metabolism, excretion, and toxicity were conducted, along with molecular docking and dynamics simulations, to evaluate protein ligand interaction stability. The results confirmed the antiviral activity of the Siparuna genus against SARS-CoV-2 targets, with 92% of the extracts maintaining over 70% cellular viability at 200 g mL 1 and 80% achieving more than 50% viral activity suppression at 50 g mL 1 . These findings highlight the potential of isoquinoline alkaloids as novel anti-coronavirus agents and support the need for further exploration, isolation, and testing of Siparuna compounds in the fight against COVID-19.