In a recent review, researchers reviewed existing literature on naturally active products with therapeutic efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Studies have reported coronavirus disease 2019 (COVID-19) breakthrough infections and multiple mutations in SARS-CoV-2 variants, warranting the development of improved vaccines and drugs against COVID-19. Researchers have highlighted the anti-SARS-CoV-2 efficacy of natural products that can potentially expand the therapeutic landscape of SARS-CoV-2 infections.
Mechanism of Anti-SARS-CoV-2 Action of Naturally Active Products
Natural products may be targeted to inhibit COVID-19 invasion and replication, regulate immune balance or reduce inflammatory factors and suppress hyperimmunity. Polyphenols, flavonoids, and alkaloids with multi-target pathways may be efficient against SARS-CoV-2. Baicalin, honokiol, curcumin, rutin, epigallocatechin gallate (ECGC), nicotinamine, kaempferol, chlorogenic acid, quercetin and glycyrrhizin can block SARS-CoV-2 entry.
Myricetin blocks NSP formation and berberine, indirubin, curcumin, β-sitosterol, betulinic acid and cordycepin inhibit the activity of Ppro and 3CLpro. Forsythosie, taraxacum sterol and parthenolide prevent systemic inflammation and organ dysfunction associated with COVID-19. Targeted CD147 inhibition has been reported for pseudopolar acid B (PAB). EGCG targets GRP78 and regulates the immune cell levels and immune factors. Astragalus polysaccharide (APS) regulates CD4+/ CD8+ ratio.
Among the natural products, EGCG, caffeic acid phenethyl ester (CPEA) and resveratrol have multi-target action and immunomodulatory effects, including stimulation of NK (natural killer) cell activity, enhancing the counts of T lymphocytes and B lymphocytes linked to neutralizing antibody (NAb) production, and regulation of CD4+/CD8+ and helper T cells (Th)1/Th2 ratios.
Baicalin has been found to inhibit 3CLpro in vitro [half maximal inhibitory concentration (IC50 0.4 μM)], and in Vero cells [half maximal effective concentration (EC50 2.9 μM)] and several RCTs have reported improved COVID-19-associated lung injury and inflammation among COVID-19 patients. In addition to inhibition of ACE2 binding and 3CLpro activity, quercetin has reduced the frequency and duration of hospitalization, invasive oxygen therapy rate among COVID-19 patients and reduced extra-articular manifestations (EMS), pain and tumor necrosis factor-alpha (TNF-α) levels in plasma among rheumatoid arthritis (RA) patients and the degree of upper respiratory tract infections.
Rutin has reduced myeloperoxidase (MPO) levels among healthy women and improved patients' neurological and inflammatory status [ox-low-density lipoprotein (LDL), nuclear factor kappa B (NF-κB) p65, TNF-α and interleukin 6 (IL-6)] in acute cerebral infarction (ACI) patients. Besides 3CLpro inhibition, berberine has reduced IL levels among acute coronary syndrome (ACS) patients.
Betulinic acid has inhibited 3CLpro (IC50 of five μM) and can activate the immune response by improving the CD4+/ CD8 + ratio. Indirubin has reduced the expression level of the proinflammatory factors IL-1β, IL-6, and TNF-α in murine models. Cordycepin has inhibited RdRp and 3CL pro with EC50 concentrations of 2 μM in SARS-CoV-2-infected Vero E6 cells.
Glycyrrhizin has inhibited SARS-COV-2 infection with EC50 of 2.4 μm in Vero E6 cells, and has been found to regulate the expression of NF-κB, TNF-α, IL-6, HMGB1 (high mobility group box 1 protein), cyclooxygenase 2 (COX-2) in rats and improved hepatic function in hepatitis B patients. Among SARS patients, glycyrrhizin reduced chest tightness, pain, cough, and improved serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in COVID-19 patients. Honokiol has inhibited furin protein (99.8%) and SARS-COV-2 infections (99.9%) at 25 μM and 50 μM concentrations, respectively, in Vero E6/TMPRSS2 cells infected with SARS-COV-2.
Conclusion
Based on the review findings, natural products such as flavonoids, polyphenols, polyterpenes, lactones and sterols can be considered COVID-19 vaccine enhancers or targeted anti-SARS-CoV-2 therapeutics. However, further research with clinical potency assessments, safety verification tests, drug interaction tests, and clinical trials are required to substantiate the multi-target and multi-pathway anti-SARS-CoV-2 effects of such natural products.
Source:
https://www.news-medical.net/news/20220810/Review-of-natural-products-with-promising-anti-SARS-CoV-2-potential.aspx