Background
Polyphenols and particularly flavonoids are of constant interest to the scientific community. Flavonoids are investigated for their biological and pharmacological purposes, notably as antioxidant, anticancer, antiviral and for their anti-inflammatory activities. Certainly, one of the best-known flavonols recognized for its therapeutic and preventive properties, is quercetin. Despite its biological interest, quercetin suffer from some drawbacks, mainly related to its bioavailability. Hence, its synthetic or biosynthetic derivatives have been the subject of intensive research. The health-promoting biological activities of flavonols and derivatives mainly arise from their capacity to disrupt the host-pathogen interactions and/or to regulate host cellular functions including oxidative processes and immunological responses. In the age of coronavirus pandemic, the anti-inflammatory and antiviral potential of flavonols should be put forward to explore these substances for decreasing the viral load and inflammatory storm caused by the infection.
Purpose of study
The present review will decipher and discuss the antioxidant, anti-inflammatory and antiviral capacities of major flavonol with a focus on the molecular basis and structure-activity relationships.
Study design
Current study used a combination of quercetin derivatives, pathway, antioxidant, anti-inflammatory, antiviral activities as keywords to retrieve the literature. This study critically reviewed the current literature and presented the ability of natural analogs of quercetin having superior antioxidant, anti-inflammatory and antiviral effects than the original molecule.
Results
This review allowed the identification of relevant key structure-activity relationship elements and highlight approaches on the mechanisms governing the antioxidant, antiviral and anti-inflammatory activities.
Conclusion
Through a critical analysis of the literature, flavonols and more precisely quercetin derivatives reviewed and found to act simultaneously on inflammation, virus and oxidative stress, three key factors that may lead to life threatening diseases.
O’nyong-nyong virus (ONNV) is a member of the reemerging arthritogenic alphaviruses that cause chronic debilitating polyarthralgia and/or polyarthritis via their tropism for the musculoskeletal system. Thus, the discovery of dual antiviral and anti-inflammatory drugs is a great challenge in this field. We investigated the effects of the common plant-derived alkaloids berberine (isoquinoline), matrine (quinolizidine), and tabersonine (indole) at a non-toxic concentration (10 μM) on a human fibroblast cell line (HS633T) infected by ONNV (MOI 1). Using qRT-PCR analyses, we measured the RNA levels of the gene coding for the viral proteins and for the host cell immune factors. These alkaloids demonstrated multifocal effects by the inhibition of viral replication, as well as the regulation of the type-I interferon antiviral signaling pathway and the inflammatory mediators and pathways. Berberine and tabersonine proved to be the more valuable compounds. The results supported the proposal that these common alkaloids may be useful scaffolds for drug discovery against arthritogenic alphavirus infection.
Both cellular and humoral immunities are critically important to control COVID19 infection but little is known about the kinetics of those responses and, in particular, in patients who will go on to develop a severe form of the disease over several weeks. We herein report the first set of data of our prospective cohort study of 90 hospitalized cases. Serological surveys were thoroughly performed over 2 month period by assessing IgG and IgM responses by immunofluorescence, immunoblot, Western blot and conventional ELISA using clinical RUN isolates of SARS-CoV-2 immobilized on 96 well plates. While the IgM and, unexpectedly, the IgG responses were readily detected early during the course of the disease (5-7 days post-first symptoms), our results (n=3-5 and over the full dilution set of the plasma 1/200 to 1/12800) demonstrated a significant decrease (over 2.5-fold) of IgG levels in severe (ICU) hospitalized patients (exemplified in patient 1) by WB and ELISA. In contrast, mild non-ICU patients had a steady and yet robust rise in their specific IgG levels against the virus. Interestingly, both responses (IgM and IgG) were initially against the nucleocapsid (50kDa band on the WB) and spreading to other major viral protein S and domains (S1 and S2. In conclusion, serological testing may be helpful for the diagnosis of patients with negative RT-PCR results and for the identification of asymptomatic cases. Moreover, medical care and protections should be maintained particularly for recovered patients (severe cases) who may remain at risk of relapsing or reinfection. Experiments to ascertain T cell responses but although their kinetics overtime are now highly warranted. All in all, these studies will help to delineate the best routes for vaccination.
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