The COVID-19 pandemic has caused a global health crisis, with no specific antiviral to treat the infection and the absence of a suitable vaccine to prevent it. While some individuals contracting the SARS-CoV-2 infection exhibit a well coordinated immune response and recover, others display a dysfunctional immune response leading to serious complications including ARDS, sepsis, MOF; associated with morbidity and mortality. Studies revealed that in patients with a dysfunctional immune response, there is a massive cytokine and chemokine release, referred to as the ‘cytokine storm’. As a result, such patients exhibit higher levels of pro-inflammatory/modulatory cytokines and chemokines like TNFα, INFγ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCSF, HGF and chemokines CXCL8, MCP1, IP10, MIP1α and MIP1β. Targeting this cytokine storm is a novel, promising treatment strategy to alleviate this excess influx of cytokines observed at the site of infection and their subsequent disastrous consequences. Natural immunosuppressant compounds, derived from plant sources like curcumin, luteolin, piperine, resveratrol are known to inhibit the production and release of pro-inflammatory cytokines and chemokines. This inhibitory effect is mediated by altering signal pathways like NF-κB, JAK/STAT, MAPK/ERK that are involved in the production and release of cytokines and chemokines. The use of these natural immunosuppressants as adjuvants to ameliorate the cytokine storm; in combination with antiviral agents and other treatment drugs currently in use presents a novel, synergistic approach for the treatment and effective cure of COVID-19. This review briefly describes the immunopathogenesis of the cytokine storm observed in SARS-CoV-2 infection and details some natural immunosuppressants that can be used as adjuvants in treating COVID-19 disease.

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.

The study of the use of nanotechnology for drug delivery has been extensive. Nanomedical approaches for therapeutics; drug delivery in particular is superior to conventional methods in that it allows for controlled targeted delivery and release, higher stability, extended circulation time, minimal side-effects, and improved pharmacokinetic clearance (of the drug) form the body, to name a few. The magnitude of COVID-19, the current ongoing pandemic has been severe; it has caused widespread the loss of human life. In individuals with severe COVID-19, immune dysregulation and a rampant state of hyperinflammation is observed. This kind of an immunopathological response is detrimental and results in rapid disease progression, development of secondary infections, sepsis and can be fatal. Several studies have pin-pointed the reason for this immune dysregulation; deviations in the signaling pathways involved in the mediation and control of immune responses. In severe COVID-19 patients, many signaling cascades including JAK/STAT, NF-κB, MAPK/ERK, TGF beta, VEGF, and Notch signaling were found to be either upregulated or inactivated. Targeting these aberrant signaling pathways in conjunction with antiviral therapy will effectuate mitigation of the hyperinflammation, hypercytokinemia, and promote faster recovery. The science of the use of nanocarriers as delivery agents to modulate these signaling pathways is not new; it has already been explored for other inflammatory diseases and in particular, cancer therapy. Numerous studies have evaluated the efficacy and potential of nanomedical approaches to modulate these signaling pathways and have been met with positive results. A treatment regime, that includes nanotherapeutics and antiviral therapies will prove effective and holds great promise for the successful treatment of COVID-19. In this article, we review different nanomedical approaches already studied for targeting aberrant signaling pathways, the host immune response to SARS-CoV-2, immunopathology and the dysregulated signaling pathways observed in severe COVID-19 and the current treatment methods in use for targeting signaling cascades in COVID-19. We then conclude by suggesting that the use of nanomedical drug delivery systems for targeting signaling pathways can be extended to effectively target the aberrant signaling pathways in COVID-19 for best treatment results.

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Tree nuts form an essential part of our diet. They are rich in proteins, fats and an array of micro and macronutrients and are also palatable and considered as a delicacy. Among all the tree nuts, the almond is often referred to as the king of nuts. This is because it contains high amounts of nutritive elements like monounsaturated fatty acids, minerals such as magnesium and copper, α-tocopherol and fiber making it an integral part of the diet. Almonds are known to reduce oxidative stress, inflammation and the risk of cardiovascular diseases and diabetes. The present study endeavored to determine the proximate composition of locally available tree almonds, Prunus amygdalus. The moisture content, ash value, iron, phosphorous, calcium, protein, fat and fiber levels were estimated by standard protocols. The results obtained were then correlated with previously described studies. The findings of this study were in line with previous studies. Locally available P. amygdalus was found to be a rich source of protein, fat, calcium and phosphorous. The moisture and ash content were low. The fiber content is moderate and amount of iron is considerably low. This makes locally available almonds a suitable, accessible and vital part of the diet.

The objective of the present study was to prepare a composite seed powder made up of seeds from plants known for their medicinal properties and to study the pharmacognostic activity of this powder. Subsequently, four sweet and three spicy food products (Indian preparation) were developed with this powder. In-vitro anti-arthritic activity of the hexane and ethyl acetate extracts was assessed by inhibition of protein denaturation method. The extracts of the seed powder were evaluated for free radical scavenging activity using DPPH. The in-vitro antimicrobial activity was determined using cup-plate method against two each gram positive and gram negative bacteria and fungi. The seed powder was used in the preparation of seven simple snack items which were evaluated on a five point-Hedonic Scale by a panel for taste, flavor, appearance texture and overall acceptance. The nutritive values of each product were computed. The hexane extract showed greater in-vitro anti-arthritic and anti-oxidant activity than that of the ethyl acetate extract. The ethyl acetate showed higher antibacterial activity against the test bacteria. All the products developed with the composite seed powder were well accepted and appreciated for their distinct flavor, good taste, appealing appearance and unmatched texture. The composite seed powder is rich in phytochemicals, hence exhibiting anti-arthritic, antioxidant and antimicrobial activity. The powder is also palatable and fit for human consumption in small amounts, as it is made from the seeds of edible fruits and vegetables.