Review of natural products with promising anti-SARS-CoV-2 potential

In a recent review published in phytotherapy researchresearchers reviewed the existing literature on naturally active products with therapeutic efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Research reports breakthrough transmission of coronavirus disease 2019 (COVID-19) and multiple mutations in SARS-CoV-2 variants, promising the development of improved vaccines and drugs against COVID-19. increase.Researchers highlight anti-SARS-CoV-2 effectiveness of A natural product that could potentially expand the treatment landscape for SARS-CoV-2 infection.

About reviews

In the current review, the researchers identified relevant studies (molecular dockingin vitro cell experimentin silico Between January 2020 and April 2022 (screening from databases such as SCI, PubMed, China National Knowledge Base (CNKI), Clinical Trials Gov, China Clinical Trials Registry (ChiCTR)).

Pathophysiology of COVID-19

SARS-CoV-2 enters host cells by transmembrane serine protease 2 (TMPRSS2) or cathepsin (Cat)B/L, and other host cells such as ACE2 (angiotensin-converting enzyme 2) and glucose-regulated protein 78 (GRP78). Identified by cellular receptors. ) and differentiation cluster 147 (CD147). SARS-CoV-2 then fuses with the host cell membrane and releases ribonucleic acid (RNA) into the host cell. Furin protease.

SARS-CoV-2 RNA is processed using host source cells by P-protease (Ppro) and 3C-like protease (3CLpro), which are cleaved into nonstructural proteins (NSPs), and RNA replication, including RNA-dependent RNA. Synthesize the necessary proteases. Polymerase (RdRp). In the host cell’s endoplasmic reticulum, viral RNA synthesizes structural proteins for virus assembly, such as the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, which then enter more human tissues. Synthesize SARS-CoV-2 progeny cells. and organs. As a result, COVID-19 causes widespread inflammation (cytokine storm) and systemic diseases such as dyspnea, hepatitis, and renal failure.

SARS-COV-2 infection causes immune dysregulation that has a profound impact on clinical recovery. SARS-CoV-2 3CLpro affects type I interferon (IFN) levels, whereas type I and III IFNs are involved in controlling viremia and regulating the immune system. In addition, SARS-CoV-2-related immune disorders can lead to autoimmune diseases and blood disorders such as hemolytic anemia.

Mechanism of Anti-SARS-CoV-2 Action of Naturally Active Products

Natural products may be aimed at inhibiting COVID-19 entry and replication, modulating immune balance or reducing inflammatory factors and suppressing hyperimmunity. Polyphenols, flavonoids, and alkaloids with multi-target pathways may be effective 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 Ppro and 3CLpro activity. Forsythia, taraxacum sterols, and parthenolide prevent systemic inflammation and organ dysfunction associated with COVID-19. Targeted CD147 inhibition has been reported with pseudopolar acid B (PAB). EGCG targets GRP78 and regulates immune cell levels and immune factors. Astragalus polysaccharide (APS) regulates the CD4+/CD8+ ratio.

Among natural products, EGCG, caffeic acid phenethyl ester (CPEA), and resveratrol have been shown to stimulate NK (natural killer) cell activity, increase the number of T and B lymphocytes bound to neutralizing antibodies. It has multitargeting and immunomodulatory effects, including (NAb) production, regulation of CD4+/CD8+ and helper T cell (Th)1/Th2 ratios.

Baicalin has been found to inhibit 3CLpro in vitro [half maximal inhibitory concentration (IC50 0.4 μM)]and in the Vero cell [half maximal effective concentration (EC50 2.9 μM)] Also, several RCTs have reported amelioration of COVID-19-related lung injury and inflammation in COVID-19 patients. In addition to inhibiting ACE2 binding and 3CLpro activity, quercetin reduced the frequency and duration of hospital stays, reduced the rate of invasive oxygen therapy in COVID-19 patients, reduced extra-articular symptoms (EMS), pain, tumor necrosis factor-alpha ( TNF-α) Plasma levels and severity of upper respiratory tract infection in patients with rheumatoid arthritis (RA).

Rutin reduced myeloperoxidase (MPO) levels in healthy women and improved neurological and inflammatory conditions in patients [ox-low-density lipoprotein (LDL), nuclear factor kappa B (NF-κB) p65, TNF-α and interleukin 6 (IL-6)] In patients with acute ischemic stroke (ACI). In addition to 3CLpro inhibition, berberine reduced her IL levels in patients with acute coronary syndrome (ACS).

Betulinic acid inhibits 3CLpro (IC50 of 5 μM) and can activate the immune response by improving the CD4+/CD8+ ratio. Indirubin reduced the expression levels of the pro-inflammatory factors IL-1β, IL-6, and TNF-α in mouse models. Cordycepin inhibited her RdRp and 3CL pro at an EC50 concentration of 2 μM in her Vero E6 cells infected with SARS-CoV-2.

Glycyrrhizin inhibits SARS-COV-2 infection with an EC50 of 2.4 μm in Vero E6 cells and modulates the expression of NF-κB, TNF-α, IL-6 and HMGB1 (high mobility group box 1 protein) I know Cyclooxygenase 2 (COX-2) in rats and improved liver function in hepatitis B patients. Among SARS patients, glycyrrhizin reduced chest tightness, pain, and cough, and improved serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in COVID-19 patients. Honokiol inhibited furin protein (99.8%) and SARS-COV-2 infection (99.9%) in Vero E6/TMPRSS2 cells infected with SARS-COV-2 at concentrations of 25 μM and 50 μM, respectively.

Conclusion

Based on the results of the review, natural products such as flavonoids, polyphenols, polyterpenes, lactones and sterols can be considered as COVID-19 vaccine enhancers or targeted anti-SARS-CoV-2 therapeutics. However, further studies on clinical efficacy evaluations, safety validation tests, drug interaction tests, and clinical trials are required to demonstrate the anti-SARS-CoV-2 efficacy of such natural products. .