BioChem, Volume 4, Issue 3 (September 2024) – 6 articles

The COVID-19 pandemic, instigated by the emergence of the novel coronavirus, SARS-CoV-2, created an incomparable global health crisis. Due to its highly virulent nature, identifying potential therapeutic agents against this lethal virus is crucial. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. To expedite the search for potential therapeutic candidates, this review delved into computational studies. Recent investigations have harnessed computational methods to identify promising inhibitors targeting PLpro, aiming to suppress the viral activity. Molecular docking techniques were employed by researchers to explore the binding sites for antiviral drugs within the catalytic region of PLpro. The review elucidates the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Through comprehensive all-atom molecular dynamics (MD) simulations, the stability of drug–PLpro complexes was assessed, providing dynamic insights into their interactions. By evaluating binding energy estimates from MD simulations, stable drug–PLpro complexes with potential antiviral properties were identified. This review offers a comprehensive overview of the potential drug/lead candidates discovered thus far against PLpro using diverse in silico methodologies, encompassing drug repurposing, structure-based, and ligand-based virtual screenings. Additionally, the identified drugs are listed based on their chemical structures and meticulously examined according to various structural parameters, such as the estimated binding free energy (ΔG), types of intermolecular interactions, and structural stability of PLpro–ligand complexes, as determined from the outcomes of the MD simulations. Underscoring the pivotal role of targeting SARS-CoV-2 PLpro in the battle against COVID-19, this review establishes a robust foundation for identifying promising antiviral drug candidates by integrating molecular dynamics simulations, structural modeling, and computational insights. The continual imperative for the improvement of existing drugs and exploring novel compounds remains paramount in the global efforts to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, underscoring the interdisciplinary synergy crucial to this endeavor. Full article

Background: Levels of chronic inflammation, oxidative stress, and neurotransmitter availability are altered in depressed patients and can be used as biological markers. This study aimed to analyze these markers in female Wistar rats under chronic inflammation induced by E. coli lipopolysaccharide (LPS), treated with aqueous extract of A. gratissima and rutin, the major flavonoid of its extract. Methods: Thirty female Wistar rats under a chronic inflammatory regimen induced by 1 mg/kg i.p. of LPS were divided into six experimental groups: control (1), treated with fluoxetine 5 mg/kg (2), rutin at 50 mg/kg (3) or 100 mg/kg (4), aqueous extract of A. gratissima 100 mg/kg (5), and co-treatment with 50 mg/kg of extract and 10 mg/kg of rutin (6). Treatments were administered by gavage for 15 days. Results: Oxidative damage to proteins and lipids was lower in group 6 compared to group 2. Pro- and anti-inflammatory cytokines increased in group 1 but not in group 2, indicating a relationship with depression. Similar effects were observed in the treated groups, showing no significant differences from group 2. Neurotransmitter levels of dopamine and serotonin were low in group 1, and all treatments effectively increased them. Additionally, A. gratissima extract at 100 ppm increased locomotor activity in planarians. Conclusions: This study demonstrates the effectiveness of the LPS induction model in subacute experimental designs and the potential antidepressant effect of the treatments due to their antioxidant and anti-inflammatory properties, and ability to increase neurotransmitter levels. Full article

Pulmonary arterial hypertension (PAH) is a progressive disorder caused by the narrowing of small blood vessels in the lungs, which, in the absence of therapies, leads to right heart failure and premature death. No cure for this devastating disorder is known. Current management therapies aim to improve symptoms, and hence, there is a need to identify novel therapeutic interventions. The major objectives of this review are to critically evaluate current treatment strategies and highlight the challenges and prospects of established drugs and natural products for the resolution of PAH. Full article

Colorectal cancer (CRC) is a prevalent and deadly tumor worldwide. Understanding the molecular mechanisms underlying CRC development will improve treatment outcomes and patient survival. Natural molecules and metabolites from plants, such as Tillandsia usneoides, reduce tumor growth by modulating glucose metabolism and increasing reactive oxygen species (ROS). To shed light on the mechanism involved in the anti-tumor effects of T. usneoides, we evaluated the cytotoxic effect of the ethanolic extract of this plant on the colon cancer cell line SW480 through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that plays a role on lipid metabolism and inflammation in cancer cells. To this end, we assessed the activation of PPARγ by T. usneoides extract in transactivation luciferase assays, as well as the cytotoxic effect of this extract on the SW480 cell line after knocking down PPARγ using shRNA. Our findings indicate that the T. usneoides extract exhibits cytotoxic effects on the SW480 cell line, potentially in the same way as PPARγ activator, pioglitazone, i.e., by increasing reactive oxygen species (ROS). In addition, both T. usneoides extract and pioglitazone exert lipogenic properties in the SW480 cells. Taken together, these results demonstrate that the T. usneoides extract decreases the viability of the colon cancer cell line SW480, at least in part, through the activation of PPARγ. This suggests the potential for further use of this plant in the treatment of other chronic diseases. Full article

Gastrointestinal diseases have been among the main concerns of medical and scientific societies for a long time. Several studies have emphasized the critical role of oxidative stress in the pathogenesis of the most common gastrointestinal diseases. To provide a comprehensive overview of gastrointestinal diseases caused by oxidative stress, their biological aspects, molecular mechanisms and specific pathways, the results of the most recent published articles from the online databases were studied considering both the upper and lower parts of the digestive tract. The results revealed that although the oxidative stress in each part of the digestive system manifests itself in a specific way, all these diseases arise from the imbalance between the generation of the reactive intermediates (especially reactive oxygen species) and the antioxidant defense system. Annual incidence and mortality statistics of gastrointestinal diseases worldwide emphasize the urgent need to find an effective and non-invasive treatment method to overcome these life-threatening problems. Therefore, in the next step, a variety of nanomedicurfines developed to treat these diseases and their effect mechanisms were investigated precisely. Furthermore, the most important nanomedicines responsive to endogenous and exogenous stimuli were evaluated in detail. This review could pave the way to open a new horizon in effectively treating gastrointestinal diseases. Full article

In the present work, methanolic extracts from thyme and dittany plants were prepared and characterized in terms of their polyphenolic content through analytical and spectrophotometric techniques. Rosmarinic acid, thymol and carvacrol were found to be the main components of the extracts, which were further biologically assessed for their antioxidant, anti-tyrosinase, anti-lipase and antibacterial activity against Gram-negative and Gram-positive bacteria. As found, thyme extracts exhibited superior antioxidant activity (SC₅₀ at 33.9 μg mL⁻¹), while dittany extracts inhibited the microbial growth to a great extent against Bacillus subtilis strain (MIC at 0.5 mg mL⁻¹) and E. coli strain (MIC at 2 mg mL⁻¹). Furthermore, the thyme extract was proven to strongly inhibit the activity of lipase from Candida rugosa (IC₅₀ at 63.9 μg mL⁻¹), comparable to the standard inhibitor orlistat, while its inhibitory effect against mushroom tyrosinase was weak. On the other hand, the dittany extract presented an inhibitory effect against the tested lipase (IC₅₀ over 500 μg mL⁻¹) and an activation effect against tyrosinase (at concentrations > 500 μg mL⁻¹). Additionally, molecular docking studies of the main compounds of the extracts showed that rosmarinic acid plays a crucial role on the inhibitory activity of the extracts against lipase, while thymol has a stronger effect on inhibiting tyrosinase. Furthermore, both extracts were employed in the preparation of gelatin-deep eutectic solvent (DES) hydrogels that were further studied for their antioxidant and antibacterial activity. The results showed that the incorporation of the extracts offered antibacterial properties to the biopolymer-based hydrogels and enhanced the antioxidant activity of gelatin up to 85%. Full article