Current Pharmaceutical Design - Volume 28, Issue 45, 2022

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a major public health threat to all countries worldwide. SARS-CoV-2 interactions with its receptor are the first step in the invasion of the host cell. The coronavirus spike protein (S) is crucial in binding to receptors on host cells. Additionally, targeting the SARS-CoV-2 viral receptors is considered a therapeutic option in this regard. In this review of literature, we summarized five potential host cell receptors, as host-cell surface bindings, including angiotensin-converting enzyme 2 (ACE2), neuropilin 1 (NRP-1), dipeptidyl peptidase 4 (DPP4), glucose regulated protein-78 (GRP78), and cluster of differentiation 147 (CD147) related to the SARS-CoV-2 infection. Among these targets, ACE2 was recognized as the main SARS-CoV-2 receptor, expressed at a low/moderate level in the human respiratory system, which is also involved in SARS-CoV-2 entrance, so the virus may utilize other secondary receptors. Besides ACE2, CD147 was discovered as a novel SARS-CoV-2 receptor, CD147 appears to be an alternate receptor for SARSCoV- 2 infection. NRP-1, as a single-transmembrane glycoprotein, has been recently found to operate as an entrance factor and enhance SARS Coronavirus 2 (SARS-CoV-2) infection under in-vitro. DPP4, which was discovered as the first gene clustered with ACE2, may serve as a potential SARS-CoV-2 spike protein binding target. GRP78 could be recognized as a secondary receptor for SARS-CoV-2 because it is widely expressed at substantially greater levels, rather than ACE2, in bronchial epithelial cells and the respiratory mucosa. This review highlights recent literature on this topic.

Background: Peritoneal adhesions (PA) are a common complication of abdominal operations. A growing body of evidence shows that inhibition of inflammation and fibrosis at sites of peritoneal damaging could prevent the development of intra-abdominal adhesions. Methods: A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords ‘postsurgical adhesion’, ‘post-operative adhesion’, ‘peritoneal adhesion’, ‘surgery-induced adhesion’ and ‘abdominal adhesion’. Studies detailing the use of pharmacological and non-pharmacological agents for peritoneal adhesion prevention were identified, and their bibliographies were thoroughly reviewed to identify further related articles. Results: Several signaling pathways, such as tumor necrosis factor-alpha, tissue plasminogen activator, and type 1 plasminogen activator inhibitor, macrophages, fibroblasts, and mesothelial cells play a key part in the development of plasminogen activator. Several therapeutic approaches based on anti-PA drug barriers and traditional herbal medicines have been developed to prevent and treat adhesion formation. In recent years, the most promising method to prevent PA is treatment using biomaterial-based barriers. Conclusion: In this review, we provide an overview of the pathophysiology of adhesion formation and various agents targeting different pathways, including chemical agents, herbal agents, physical barriers, and clinical trials concerning this matter.

Insomnia is well-known as trouble in sleeping and enormously influences human life due to the shortage of sleep. Reactive Oxygen Species (ROS) accrue in neurons during the waking state, and sleep has a defensive role against oxidative damage and dissipates ROS in the brain. In contrast, insomnia is the source of inequity between ROS generation and removal by an endogenous antioxidant defense system. The relationship between insomnia, depression, and anxiety disorders damages the cardiovascular systems' immune mechanisms and functions. Traditionally, polysomnography is used in the diagnosis of insomnia. This technique is complex, with a long time overhead. In this work, we have proposed a novel machine learning-based automatic detection system using the R-R intervals extracted from a single-lead electrocardiograph (ECG). Additionally, we aimed to explore the role of oxidative stress and inflammation in sleeping disorders and cardiovascular diseases, antioxidants’ effects, and the psychopharmacological effect of herbal medicine. This work has been carried out in steps, which include collecting the ECG signal for normal and insomnia subjects, analyzing the signal, and finally, automatic classification. We used two approaches, including subjects (normal and insomnia), two sleep stages, i.e., wake and rapid eye movement, and three Machine Learning (ML)-based classifiers to complete the classification. A total number of 3000 ECG segments were collected from 18 subjects. Furthermore, using the theranostics approach, the role of mitochondrial dysfunction causing oxidative stress and inflammatory response in insomnia and cardiovascular diseases was explored. The data from various databases on the mechanism of action of different herbal medicines in insomnia and cardiovascular diseases with antioxidant and antidepressant activities were also retrieved. Random Forest (RF) classifier has shown the highest accuracy (subjects: 87.10% and sleep stage: 88.30%) compared to the Decision Tree (DT) and Support Vector Machine (SVM). The results revealed that the suggested method could perform well in classifying the subjects and sleep stages. Additionally, a random forest machine learning-based classifier could be helpful in the clinical discovery of sleep complications, including insomnia. The evidence retrieved from the databases showed that herbal medicine contains numerous phytochemical bioactives and has multimodal cellular mechanisms of action, viz., antioxidant, anti-inflammatory, vasorelaxant, detoxifier, antidepressant, anxiolytic, and cell-rejuvenator properties. Other herbal medicines have a GABA-A receptor agonist effect. Hence, we recommend that the theranostics approach has potential and can be adopted for future research to improve the quality of life of humans.

Aim: The cytochrome P450 enzymes play a significant role in regulating cellular and physiological processes by activating endogenous compounds. They also play an essential role in the detoxification process of xenobiotics. Flavonoids belong to a class of polyphenols found in food, such as vegetables, red wine, beer, and fruits, which modulate biological functions in the body. Methods: The inhibition of CYP1A1 and CYP1B1 using nutritional sources has been reported as a strategy for cancer prevention. This study investigated the interactions of selected flavonoids binding to the cytochrome P450 enzymes (CYP1A1 and CYP1B1) and their ADMET properties in silico. From docking studies, our findings showed flavonoids, isorhamnetin and pedalitin, to have the strongest binding energies in the crystal structures 6DWM and 6IQ5. Results: The amino acid residues Asp 313 and Phe 224 in 6DWM interacted with all the ligands investigated, and Ala 330 in 6IQ5 interacted with all the ligands examined. The ligands did not violate any drug-likeness parameters. Conclusion: These data suggest roles for isorhamnetin and pedalitin as potential precursors for natural product- derived therapies.