Anti-inflammatory alkaloids targeting IL-1 against Respiratory Viral infections: A Special insight into drug development against SARS-CoV 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the deadliest viruses among respiratory viruses which resulted in COVID-19 pandemic. The virus gets transmitted by the nasal route and moves down to the trachea, bronchi, and then to the lungs. Once replicated inside the alveolar cells, the SARS-CoV-2 makes the membrane of the alveolar sac porous, which causes the leaking of plasma from surrounding blood vessels into the alveolar sac leading to its buildup. This process results in the production of pro-inflammatory cytokines like interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α) by the helper T-cells at the site of the infection, causing difficulty in breathing. Plant-based alkaloids can be promising to treat viral infections. Plants have contributed to drug development against viruses like Herpes simplex virus (HSV), Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and viruses that cause respiratory diseases in humans. Plant alkaloids, either in the form of extract, infusion, or powder, have shown potential in treating viral diseases mainly by targeting the replication of viruses. Alkaloids like Tetrandrine, Oxymatrine, and Berberine have been shown to have a positive role in mediating pro-inflammatory cytokines like IL-1. These alkaloids thus inactivate the nuclear factor kappa-B (NF-kB) pathway, inhibiting the expression of its targeted genes, IL-1β and TNF-α. This inactivation of NF-kB results in reduced levels of IL-1 and TNF-α, and consequently reduced inflammation, decreasing the stress on the immune cells and increasing the ability of the patient to fight the infection. Despite vaccine development for SARS-CoV-2, the virus is continuously evolving into new varieties, posing a threat to humans and it is necessary to develop effective drug discovery programs. Natural products can pave the way in this regard. This review can contribute towards safer drug development against SARS-CoV-2, combating the threat of the ever-emerging variants of this virus.