This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 μM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1 μM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1 μM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4 μM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of −6.7 kcal/mol and −7.5 kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19.

The aim of this research was to evaluate the effect of ultrasound pretreatment on enzymatic hydrolysis with Flavourzyme® and Alcalase® enzymes and the ACE-inhibitory activity and the antioxidant capacity of protein hydrolysates of Erythrina edulis. A protein concentration of 78.8% was obtained after sonicating the protein solutions (10%, w/v) for 10 min at 80 kHz and 100% amplitude. The ultrasonic pretreatment (UP) increased the degree of hydrolysis (47.7%) up to 70 min, the IC50 values in both samples [with (UP) and without pretreatment (WP)] were 100 μg/mL, and the UP samples presented the highest percentage of inhibition at 57.3%. The UP hydrolysates showed the highest (p < 0.05) antioxidant (ABTS*) and radical (DPPH*) - scavenging activities, with IC50 values ranging from 64.52 to 77.62 μg/mL and from 151.13 to 173.22 μg/mL, respectively. In SDS-PAGE, the hydrolysates UP exhibited low molecular weight bands (8 - 20 kDa). The results of both, antioxidants and antihypertensive activities obtained in vitro, showed a higher percentage of activity for the peptides obtained after pretreatment with ultrasound than for those obtained without the use of ultrasound prior to enzymatic hydrolysis.

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This study aimed to evaluate the release of active components with antioxidant and antihypertensive capacity from encapsulated extracts of the peel and seeds of Gulupa (Passiflora edulis f. edulis) and Cholupa (Passiflora maliformis) in an in vitro gastrointestinal digestion model. Microencapsulated extracts were prepared with enzymatically modified rice starch as the encapsulating material and ethanol extracts of seeds and peel of P. edulis f. edulis and P. maliformis as encapsulated material. Microcapsule characterization was performed by scanning electron microscopy with values of 4.54-5.13 μm and ξ potential values of -6.34 mV and -6.66 mV. Dynamic light scattering (DLS) analysis was conducted with polydispersion values from 1.33 to 1.51, and dispersion stability analysis was also conducted. The total phenol content and antioxidant activities (ABTS, DPPH, and FRAP) and ACE inhibitory activity (in vitro antihypertensive activity) were evaluated after each stage of digestion, with values greater than 80% of activity before gastrointestinal transit and with values greater than 55% activity after the end of gastrointestinal transit. Gastrointestinal evaluation of the encapsulated extracts was performed with an ex vivo model using pig intestines and simulating the conditions of digestion in three phases: the gastric (pH 2.0 with 1.0 M HCl þ0.5 g/L pepsin), enteric (pH 8.0 with Krebs solution þ1.0 mL/L bile) and final enteric (pH 7.5 Krebs solution only) phases. The microencapsulation of passionflower extracts showed good behavior against changes in pH and enzymatic activities throughout digestion, thus promoting a controlled release and targeted delivery of bioactive compounds, undergoing a paracellular mechanism through the intestinal barrier to preserve the antioxidant activity and ACE inhibitory that was shown by the extracts before encapsulation of the material.

Introduction: SARS-CoV-2 has caused a pandemic of historic proportions and continues to spread worldwide. Currently, there is no effective therapy against this virus. This article evaluated the in vitro antiviral effect of Atorvastatin against SARS-CoV-2 and also identified the interaction affinity between Atorvastatin and three SARS-CoV-2 proteins, using in silico structure-based molecular docking approach. Materials and methods: The antiviral activity of Atorvastatin against SARS-CoV-2 was evaluated by three different treatment strategies using a clinical isolate of SARS-CoV-2. The interaction of Atorvastatin with Spike, RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) was evaluated by molecular docking. Results: Atorvastatin showed anti-SARS-CoV-2 activity of 79%, 54.8%, 22.6% and 25% at 31.2, 15.6, 7.9, and 3.9 µM, respectively, by pre-post-treatment strategy. In addition, atorvastatin demonstrated an antiviral effect of 26.9% at 31.2 µM by pre-infection treatment. This compound also inhibited SARS-CoV-2 in 66.9%, 75%, 27.9% and 29.2% at concentrations of 31.2, 15.6, 7.9, and 3.9 µM, respectively, by post-infection treatment. The interaction of atorvastatin with SARS-CoV-2 Spike, RdRp and 3CL protease yielded a binding affinity of -8.5 Kcal/mol, -6.2 Kcal/mol, and -7.5 Kcal/mol, respectively. Conclusion: Our study demonstrated the in vitro anti-SARS-CoV-2 activity of Atorvastatin, mainly against the late steps of the viral replicative cycle. A favorable binding affinity with viral proteins by bioinformatics methods was also shown. Due to its low cost, availability, well-established safety and tolerability, and the extensive clinical experience of atorvastatin, it could prove valuable in reducing morbidity and mortality from COVID-19.