Beyond the pandemic: Natural products against coronavirus cytokine storm

Despite the COVID-19 pandemic being over, efforts at identifying pharmacological strategies against different components of its pathogenesis are still being explored. Acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection has been linked to cytokine storm and the accompanying exaggerated release of pro-inflammatory cytokines [1]. In this regard, anti-inflammatory strategies such as the use of dexamethasone have been shown to provide some benefits in the treatment of COVID-19 [2]. Consequently, we investigated some natural compounds as potential pharmacological strategies to combat cytokine storm induced by SARS-CoV-2 and other coronaviruses. To achieve this, human peripheral blood mononuclear cells (PBMCs) were co-cultured with human bronchial epithelial (BEAS-2B) cells, which were then stimulated with SARS-CoV-2 spike protein (S1). Culture supernatants were analysed for levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β and IL-8. Studies on selected natural compounds revealed that garcinoic acid (from Garcinia kola Heckel), skimmianine (from Zanthoxylum zanthoxylodes (Lam.) B.Zepernick & Timler), andrographolide (from Andrographis paniculata (Burm.f.) Wall. ex Nees), eucalyptol (from Eucalyptus globulus Labill.), and curcumin (from Curcuma longa L.) inhibited S1-induced increased production of pro-inflammatory cytokines in PBMC/BEAS-2B co-culture. Incubation of the co-culture with these compounds also resulted in reduced damage to BEAS-2B cells. The potentials of these compounds as anti-inflammatory strategies in reducing symptoms of severe coronavirus infections, including ARDS will be presented. The relevance of these studies in preparing for future coronavirus pandemics will also be discussed.