A comprehensive review of phytochemicals of Withania somnifera (L.) Dunal (Solanaceae) as antiviral therapeutics

Viruses have caused millions and billions of infections and high mortality rates without successful immunization due to a lack of antiviral drugs approved for clinical use. Therefore, the discovery of novel antiviral drugs is impertinent and natural products are excellent alternative sources. Withania somnifera (L.) Dunal (Solanaceae) is recognized as one of the most significant herbs in the Ayurvedic system and it had been utilized in various biological actions for more than 3000 years. This review aimed to discuss the therapeutic effects and associated molecular mechanisms of Withania somnifera (WS) and its phytochemicals, withanolides against various viruses in preclinical and clinical settings towards developing potential inhibitors which could target virus proteins or their respective host cell receptors. WS was reported to attenuate coronavirus disease 2019 (COVID-19), serve as a potential ligand against the herpes simplex virus (HSV) DNA polymerase, suppress Alzheimer’s disease progression by inhibiting the cytotoxicity induced by the human immunodeficiency virus 1 (HIV-1)-activated beta-amyloid (Aβ), and attenuate the neuraminidase activity of H1N1 influenza. WS root extracts have also reduced the mortality rates and stress levels in tilapia infected with tilapia lake virus (TiLV), and stimulated antiviral nitric oxide formation in chicks infected with infectious bursal disease (IBD). With increasing evidence from previous literatures, further in vitro and in vivo investigations of WS against other viral infections may provide promising results. Graphical Abstract Article highlights Withanolides have been predicted to inhibit SARS-CoV-2 viral proteins. Withaferin A has been predicted to alter HSV DNA polymerase’s binding conformation. Withaferin A also suppressed HIV-1 transcription and replication.