Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Non-Structural Protein 16 (nsp-16) is a viral RNA methyltransferase (MTase) and a key target for coronavirus drug development.
• SARS-CoV-2, the virus responsible for COVID-19, relies on nsp-16 for its replication.

Purpose of the Study:

• To identify potential drug candidates for inhibiting SARS-CoV-2 nsp-16 through a virtual drug repurposing approach.
• To evaluate the efficacy of FDA-approved drugs and nucleoside analogs as nsp-16 inhibitors.

Main Methods:

• Drug shape-based screening using sinefungin as a template.
• Molecular docking to determine binding energies and interaction modes.
• Molecular dynamics (MD) simulations to assess drug stability and effectiveness in a realistic environment.

Main Results:

• Raltegravir and Maraviroc demonstrated strong binding affinity to the nsp-16 active site, outperforming the known inhibitor sinefungin.
• MD simulations indicated that Raltegravir and Maraviroc are more effective than sinefungin in inhibiting the nsp-16 enzyme.
• These compounds showed significant potential as SARS-CoV-2 nsp-16 inhibitors.

Conclusions:

• Raltegravir and Maraviroc are promising drug candidates for inhibiting SARS-CoV-2 nsp-16.
• Further in vitro, in vivo, and clinical studies are warranted to confirm the therapeutic potential of Raltegravir and Maraviroc for COVID-19 treatment.