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The fear of SARS-CoV-2 infection is due to its high mortality related to seasonal flu. To date, few medicines have been developed to significantly reduce the mortality of the severe COVID-19 patients, especially those requiring tracheal intubation. The severity and mortality of SARS-CoV-2 infection not only depend on the viral virulence, but are primarily determined by the cytokine storm and the destructive inflammation driven by the host immune reaction. Thus, to target the host immune response might be a better strategy to combat this pandemic. Melatonin is a molecule with multiple activities on a virus infection. These include that it downregulates the overreaction of innate immune response to suppress inflammation, promotes the adaptive immune reaction to enhance antibody formation, inhibits the entrance of the virus into the cell as well as limits its replication. These render it a potentially excellent candidate for treatment of the severe COVID-19 cases. Several clinical trials have confirmed that melatonin when added to the conventional therapy significantly reduces the mortality of the severe COVID-19 patients. The cost of melatonin is a small fraction of those medications approved by FDA for emergency use to treat COVID-19. Because of its self-administered, low cost and high safety margin, melatonin could be made available to every country in the world at an affordable cost. We recommend melatonin be used to treat severe COVID-19 patients with the intent of reducing mortality. If successful, it would make the SARS-CoV-2 pandemic less fearful and help to return life back to normalcy. [ABSTRACT FROM AUTHOR]

Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. The literature search resulted in numerous in vitro , in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm. [Display omitted] [ABSTRACT FROM AUTHOR]

It has become evident that the actions of pro-inflammatory cytokines and/or the development of a cytokine storm are responsible for the occurrence of severe COVID-19 during SARS-CoV-2 infection. Although immunomodulatory mechanisms vary among viruses, the activation of multiple TLRs that occurs primarily through the recruitment of adapter proteins such as MyD88 and TRIF contributes to the induction of a cytokine storm. Based on this, controlling the robust production of pro-inflammatory cytokines by macrophages may be applicable as a cellular approach to investigate potential cytokine-targeted therapies against COVID-19. In the current study, we utilized TLR2/MyD88 and TLR3/TRIF co-activated macrophages and evaluated the anti-cytokine storm effect of the traditional Chinese medicine (TCM) formula Babaodan (BBD). An RNA-seq-based transcriptomic approach was used to determine the molecular mode of action. Additionally, we evaluated the anti-inflammatory activity of BBD in vivo using a mouse model of post-viral bacterial infection-induced pneumonia and seven severely ill COVID-19 patients. Our study reveals the protective role of BBD against excessive immune responses in macrophages, where the underlying mechanisms involve the inhibition of the NF-κB and MAPK signaling pathways. In vivo, BBD significantly inhibited the release of IL-6, thus resulting in increased survival rates in mice. Based on limited data, we demonstrated that severely ill COVID-19 patients benefited from BBD treatment due to a reduction in the overproduction of IL-6. In conclusion, our study indicated that BBD controls excessive immune responses and may thus represent a cytokine-targeted agent that could be considered to treating COVID-19. [Display omitted] • Cytokine-targeted therapeutic strategies to reduce lung inflammatory injury have been proposed for the treatment of patients with severe COVID-19. • TCM within the "heat-clearing and detoxifying (qingre jiedu)" category have been demonstrated to exert strong anti-inflammatory activities. • Baobadan (BBD) exerts pronounced anti-inflammatory effects on TLR1/2 and TLR3 dual activated macrophages that are associated with NF-κB and MAPKs. • BBD protects mice from excessive cytokine production and inflammatory lung injury. • Based on limited data, BBD appears to reduce the overproduction of IL-6 in severely ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

• Drugs to attenuate cytokine storm in COVID-19 are unavailable. • Canagliflozin attenuated inflammatory cytokine storm in LPS-treated mice.. • Atomized administration of Canagliflozin also exhibited anti-inflammatory effects. To date, drugs to attenuate cytokine storm in severe cases of Corona Virus Disease 2019 (COVID-19) are not available. In this study, we investigated the effects of intragastric and atomized administration of canagliflozin (CAN) on cytokine storm in lung tissues of lipopolysaccharides (LPS)-induced mice. Results showed that intragastric administration of CAN significantly and widely inhibited the production of inflammatory cytokines in lung tissues of LPS-induced sepsis mice. Simultaneously, intragastric administration of CAN significantly improved inflammatory pathological changes of lung tissues. Atomized administration of CAN also exhibited similar effects in LPS-induced sepsis mice. Furthermore, CAN significantly inhibited hypoxia inducible factor 1α (HIF-1α) and phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) protein levels in LPS-treated lung tissues. These results indicated that CAN might attenuate cytokine storm and reduce the inflammatory symptoms in critical cases in COVID-19. Its action mechanism might involve the regulation of HIF-1α and glycolysis in vivo. However, further studies about clinical application and mechanism analysis should be validated in the future. [ABSTRACT FROM AUTHOR]