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The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration. In Brief • Curcumin has a wide range of pharmacological effects against a variety of pathologies with limitations such as poor aqueous solubility, extensive metabolism and rapid elimination. • Nanoscale techniques have been used to overcome these pharmacokinetic limitations, with encouraging results in both laboratory experiments and in vivo. • The observed decrease in gene expression and secretion of inflammatory biomarkers (implicated in the cytokine storm seen in severe COVID-19 cases), as well as the increase in lymphocyte count, have provided evidence for the therapeutic potential of nanocurcumin. [Display omitted] [ABSTRACT FROM AUTHOR]

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19. • BromAc is a strong mucolytic for COVID-19 sputum ex vivo. • Select chemokines and cytokines were downregulated following BromAc exposure. • Mucolytic and anti-inflammatory effects of BromAc were dose-dependent. • Further assessment of BromAc in COVID-19 clinical trials is warranted. [ABSTRACT FROM AUTHOR]

• Propolis, made by bees from bioactive plant resins, has antiviral activity. • Propolis potentially can interfere with host cell invasion by SARS-CoV-2. • Propolis blocks proinflammatory PAK1, a kinase highly expressed in COVID19 patients. • Standardized propolis has consistent properties for lab and clinical research. • Propolis is a safe widely consumed functional food with medicinal properties. Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. This mechanism involves PAK1 overexpression, which is a kinase that mediates coronavirus-induced lung inflammation, fibrosis, and immune system suppression. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-α. This immunoregulation involves monocytes and macrophages, as well as Jak2/STAT3, NF-kB, and inflammasome pathways, reducing the risk of cytokine storm syndrome, a major mortality factor in advanced COVID-19 disease. Propolis has also shown promise as an aid in the treatment of various of the comorbidities that are particularly dangerous in COVID-19 patients, including respiratory diseases, hypertension, diabetes, and cancer. Standardized propolis products with consistent bioactive properties are now available. Given the current emergency caused by the COVID-19 pandemic and limited therapeutic options, propolis is presented as a promising and relevant therapeutic option that is safe, easy to administrate orally and is readily available as a natural supplement and functional food. [ABSTRACT FROM AUTHOR]