Biosynthesis of Nimbin and the Metabolic Pathway: A Focus on its Antiviral Properties

Nimbin, a triterpenoid limonoid from Azadirachta indica (Neem), is traditionally known for its diverse pharmacological potential, including antimicrobial and anti-inflammatory properties. However, it has recently gained wider scientific attention for its ability to protect the host cell from viral entry, suppress viral replication, and modulate immune responses against viral infections, such as Herpes simplex virus, Dengue virus, and SARS-CoV-2.

This review compiles and evaluates current findings on nimbin's medicinal properties, with a focus on its antiviral mechanisms, biosynthetic pathways, and therapeutic prospects.

Nimbin achieves this by targeting key viral proteins such as spike glycoproteins and NS2B-NS3 proteases, as well as host receptors like ACE2, thereby disrupting the viral life cycle. It is also reported to interfere with the replication process of viruses by inhibition of protease enzymes and proteins essential for polyprotein processing and modulation pathways critical for viral genome replication. Apart from the antiviral activity, it also exhibits anticancer, antioxidant, antifungal, and insecticidal properties. The Mevalonate or Methylerythritol phosphate pathway, or a combination of both are key process involved in the biosynthesis of nimbin, occurring in either a localized form in plastids or distributed across the cytoplasm, endoplasmic reticulum, and peroxisomes. Advances in the synthesis of water-soluble, non-toxic 'Carbon dots' containing active nimbin biomolecules, and nanoencapsulation for better drug delivery processes will likely enhance the biomedical traits of nimbin and its derivatives to serve as a multifaceted candidate for antiviral therapy and sources of drugs.

Although promising, further pharmacokinetic profiling, toxicological assessment, and clinical validation are essential to translate nimbin into an effective phytopharmaceutical agent. To improve the therapeutic efficacy and bioavailability of drugs, future studies should investigate novel nanoformulations and tailored drug delivery techniques.