Dra. Gerli-Candia, Lorena

Silymarin derivatives, renowned for their antioxidant and hepatoprotective properties, have recently emerged as promising candidates for anticancer therapy due to their potential to modulate critical oncogenic pathways. Four silymarin derivatives (silibinin, isosilibinin, silicristin, silidianin), known for liver protection, were explored as potential multi-target anticancer agents using computational methods. Molecular docking against key cancer proteins (AKT, PI3K, PARP, mTOR, GSK3-β, PDK1, PAK4) identified silicristin as the strongest binder, confirmed by stable molecular dynamics simulations and favorable binding energy (ΔG = −125.78 kcal/mol via MM-GBSA). Silidianin showed the highest chemical reactivity (smallest HOMO–LUMO gap: 0.1535 eV). All compounds displayed promising ADMET profiles: high intestinal absorption, low blood-brain barrier penetration, and silidianin exhibited the lowest acute toxicity (LD50 = 10,000 mg/kg). While potential immunotoxicity was noted, silicristin and silidianin emerged as the most promising candidates due to their strong target binding, stability, reactivity, and favorable safety predictions, warranting further experimental validation. This multi-scale computational study identifies silicristin and silidianin as promising multi-target anticancer candidates. Their stability, favorable electronic profiles, and low predicted toxicity support further in vitro and in vivo validation.

The largest threat to civilization since the Second World War is the spread of the new coronavirus disease (COVID-19). Therefore, there is an urgent need for innovative therapeutic medicines to treat COVID-19. Reusing bio-actives is a workable and efficient strategy in the battle against new epidemics because the process of developing new drugs is time-consuming. This research aimed to identify which herbal remedies had the highest affinity for the receptor and assess a variety of them for potential targets to suppress the SARS-CoV-2 Mpro. The use of AutoDock Vina for structure-based virtual screening was done first due to the importance of protein interactions in the development of drugs. Molecular docking was used in the comparative study to assess 89 different chemicals from medicinal herbs. To anticipate their effectiveness against the primary protease of SARS-CoV-2, more analysis was done on the ADMET profile, drug-likeness, and Lipinski’s rule of five. The next step involved three replicas of 100 ns-long molecular dynamics simulations on the potential candidates, which were preceded by calculations of the binding free energy of MM-GBSA. The outcomes showed that Achyrodimer A, Cinchonain Ib, Symphonone F, and Lupeol acetate all performed well and had the highest 6LU7 binding affinities. Using RMSD, RMSF, and protein-ligand interactions, the stability of the protein-ligand complex was assessed. The studies indicate that bioactive substances obtained from herbal medicines may function as a COVID-19 therapeutic agent, necessitating additional wet lab research to confirm their therapeutic potential, efficacy, and pharmacological capacity against the condition.

COVID-19 is a zoonotic viral disease caused by the SARS-CoV-2 virus. Its abrupt outbreak has caused a tremendous challenge to public health systems due to the rapid spread of the virus. In this sense, a great deal of work has been focused on finding substances from herbal plants to be used against this virus. In order to investigate the molecular interactions between natural metabolites from Algerian herbal plants and the SARS-CoV-2 protease Mpro, computational docking and molecular dynamics were used, also the drug likeness degree and in silico ADMET prediction were carried out in this study. warfarin and catalponol preferentially binds to a pocket of the SARS-Cov-2 Mpro active site that is made up of residues His 41 to Glu 166 and Leu 27 to His 163 with a relatively low binding energy of -7.1 and -6.6 kcal/mol respectively. Dynamic molecular assay further established that only warfarin managed to stay in the active site. The results suggest that warfarin may be an interesting candidate for development as a medical treatment of COVID-19 and more research is proposed, without disregarding its toxicity which deserves to be well studied.