Identification of phytochemicals as potential therapeutic agents that binds to Nsp15 protein target of coronavirus (SARS-CoV-2) that are capable of inhibiting virus replication

Phytomedicine. 2021 May;85:153317. doi: 10.1016/j.phymed.2020.153317. Epub 2020 Sep 3.


Background: Coronavirus disease 2019 (COVID-19) playing havoc across the globe caused 585,727 deaths and 13,616,593 confirmed cases so far as per World Health Organization data released till 17th July 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is responsible for causing this pandemic across different continents. It is not only impacting the world economy but also quarantined millions of people in their homes or hospitals.

Purpose: At present, there is no Food and Drug Administration-approved drug or vaccine available to treat this disease. Still, people are trying various pre-existing medicines that are known to have anti-viral or anti-parasitic effects. In view of this, the present study aimed to study the binding potential of various phytochemicals present in multiple natural plant extract as a secondary metabolite to non-structural protein 15 (Nsp15) protein, a drug target known to play a crucial role in virulence of coronavirus.

Method: Nsp15 protein was selected because it shows 89% similarity to the other SARS-CoV, which caused the earlier outbreak. The assumption is that inhibition of Nsp15 slowdowns the viral replication. Phytochemicals are selected as these are present in various plant parts (seed, flower, roots, etc.), which are used in different food cuisines in different geographical regions across the globe. The molecular docking approach was performed using two different software, i.e., Autodock, and Swissdock, to study the interaction of various phytochemicals with Nsp15 protein. Hydroxychloroquine is used as a positive control as it is used by medical professionals showing some positive effects in dealing with coronavirus.

Results: The present study demonstrated the binding potential of approximately 50 phytochemicals with Nsp15 and capable of inhibiting the viral replication, although in vitro and in vivo tests are required to confirm these findings.

Conclusions: In conclusion, the present study successfully demonstrated the binding of phytochemicals such as sarsasapogenin, ursonic acid, curcumin, ajmalicine, novobiocin, silymarin and aranotin, piperine, gingerol, rosmarinic acid, and alpha terpinyl acetate to Nsp15 viral protein and they might play a key role in inhibiting SARS-CoV-2 replication.

Keywords: Coronavirus disease 2019 (COVID-19); Molecular docking; Non-structural protein 15 (Nsp15); Phytochemicals; SARS-CoV-2; Sarsasapogenin.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Endoribonucleases / antagonists & inhibitors*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Phytochemicals / pharmacology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / physiology
  • Software
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Phytochemicals
  • Viral Nonstructural Proteins
  • Endoribonucleases
  • nidoviral uridylate-specific endoribonuclease