Phytotherapeutic Potential of Azadirachta indica: Modulating SARS-CoV-2 Viral Entry and the Endothelial Pro-inflammatory Cascade

Azadirachta indica (neem) is a versatile medicinal plant with potent antiviral, anti-inflammatory, and immunomodulatory properties. This study evaluates its phytotherapeutic potential in modulating SARS-CoV-2 entry and the subsequent pro-inflammatory cascade. Bioactive constituents, including azadirachtin, nimbolide, and quercetin, interact with the viral spike protein and host receptors like ACE2 and Neuropilin-1 (NRP1) to block viral attachment. Furthermore, neem extracts significantly reduce viral replication in human lung cells. By inhibiting the NF-κB pathway and reducing pro-inflammatory cytokines such as TNF-α and IL-6, neem helps mitigate the "cytokine storm" and prevents multi-organ dysfunction associated with severe COVID-19. Its antioxidant capacity further protects the vascular endothelium from oxidative stress and tissue damage. While in vitro and in vivo results are promising, clinical trials are essential to confirm the safety and efficacy of neem as an affordable, sustainable adjuvant in evidence-based COVID-19 management.