Glycyrrhizin and boswellic acids, the golden nutraceuticals: multitargeting for treatment of mild–moderate COVID-19 and prevention of post-COVID cognitive impairment

Abstract

Breakthrough infections have been reported in fully vaccinated persons. Furthermore, rebound symptoms have been reported following the new FDA granted emergency use to combat SARS-CoV-2. Glycyrrhizin (GR) and boswellic acids (BAs) combination has been shown to have highly successful actions against COVID-19 in our recent clinical trial. However, the study is limited by the small sample size, and therefore, the aim of this article is to comprehensively evaluate recent evidence on the efficacy of GR and BAs in preventing the development of COVID-19 in patients with mild and moderate infections and in preventing post-COVID-19 cognitive impairment, which is the most important symptom after recovery from Covid-19 disease. We have reviewed and discussed information published since the outbreak of the COVID-19 pandemic until July 2022 on preclinical (in vivo, in vivo and bioinformatics) and clinical studies related to the antiviral, anti-inflammatory and immunomodulatory activity of Gr and BAs. Sixteen studies were performed to determine the efficacy of GR against SARS-CoV-2. Ten studies were used primarily for in vitro and in vivo assays and six used molecular docking studies. However, the antiviral activity of BAs against SARS-CoV-2 was determined in only five studies using molecular modeling and bioinformatics. All these studies confirmed that GR n and BAs have strong antiviral activity and can be used as a therapeutic agent for COVID-19 and as a protective agent against SARS-CoV-2. They may act by inhibiting the main protease SARS-CoV-2 (Mpro) responsible for replication and blocking spike protein-mediated cell entry. Only seven rigorously designed clinical trials regarding the usefulness of GR, BAs or their combinations in the treatment of COVID-19 have been published as of July 2022. Although there is no clinical study regarding the treatment of cognitive impairment after COVID-19 that has been published so far, several preclinical and clinical studies have demonstrated the potential effect of GR and BAs in the prevention and treatment of cognitive impairment by inhibiting the activity of several molecules that activate inflammatory signaling pathway. In conclusion, the findings of our study documented the beneficial use of GR and BAs to treat SARS-CoV-2 and its variants and prevent post-COVID cognitive impairment. However, it warrants further studies with a larger randomized sample size to ensure that the studies have sufficient evidence of benefits against COVID-19 and post-COVID-19 symptoms.

Strategies for the Management of Spike Protein-Related Pathology

“…The pharmaceutical compounds with plausible applicability for the treatment of long Covid, and post-injection syndrome are listed in Table 1. Licorice Immunomodulatory, anti-inflammatory [323] [324-328] Proxy (inhibits virus in vitro [328]) Cardamom Anti-inflammatory (IVO [329] [329] Proxy (lowers inflammatory markers) [329] Cloves Antithrombotic, anti-inflammatory [330], Blocks S1-ACE2 interaction (IS, CFA) [331], stimulates autophagy [332] [330] Prevents post-Covid cognitive impairment [333] Ginger [334,335] Proxy. Reduced hospitalization period in SC2 infection [336] Garlic Immunomodulatory [337] [337-339] Proxy (faster recovery from C19) [340] Thyme Antioxidant, nutrient rich, anti-inflammatory [341] [342] Positive impact [289] Propolis ACE2 signalling pathways (IS [343],IVT,IVO) [344,345] Immunomodulation [346] [ 344,347,348] Meta-analysis reveals propolis and honey could probably improve clinical Covid-19 symptoms and decrease viral clearance time [343] Serratiopeptase Fibrinolytic [349] [350]…”

Sharps Injury Rates Reported Among US Workers

“…Hospitals and medical environments should continue to provide necessary protection from SIs, including closable, puncture-resistant, and clearly marked sharps containers and safety-engineered needles 4,10,11,17,48,49 . Although these protections could not be assessed in this study, they are important safety measures to consider.…”

“…In addition to actual risk, the perception of risk upon sustaining an SI can result in severe and prolonged mental distress, including depression, anxiety, and posttraumatic stress disorder 8,9 . Proper sharps handling is shown to greatly reduce staff absence from related psychological and physical burdens of these injuries 4,10–18 . Sharps injuries also generate significant direct and indirect costs due to lost productivity and postexposure diagnostic and prophylactic protocols 19 .…”

Strategies for the Management of Spike Protein-Related Pathology

“…Reduction in fatigue (not longcovid related) 196 improved oxygenation, decrease in inflammatory markers and a faster recovery were observed in initial covid-19 infection (proxy measure for long-covid) 197 Improvement in general fatigue symptioms when combined with larginine 198 Significant improvement 199 Vitamin K2 Immunomodulatory Proxy (inhibits virus in vitro 296 ) Cardamom Anti-inflammatory (IVO 297 297 Proxy (lowers inflammatory markers) 297 Cloves Antithrombotic, antiinflammatory 298 , Blocks S1-ACE2 interaction (IS, CFA) 299 , stimulates autophagy 300 298 Prevents post-Covid cognitive impairment 301 Ginger 302,303…”