Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp

Area of Science:

• Virology
• Medicinal Chemistry
• Drug Discovery

Background:

• Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, necessitates urgent therapeutic interventions.
• RNA-dependent RNA polymerase (RdRp) is a critical enzyme in the SARS-CoV-2 life cycle and a prime target for antiviral drug development.

Purpose of the Study:

• To screen a library of quinoline and quinazoline derivatives for inhibitory activity against SARS-CoV-2 RdRp.
• To identify novel compounds with potent antiviral activity and low cytotoxicity for potential COVID-19 treatment.

Main Methods:

• A cell-based assay was employed to screen 101 quinoline and quinazoline derivatives against SARS-CoV-2 RdRp.
• Inhibition of RNA synthesis and cytotoxicity were evaluated for the screened compounds.

Main Results:

• Three compounds, I-13e, I-13h, and I-13i, demonstrated significant inhibition of SARS-CoV-2 RdRp-driven RNA synthesis with low cytotoxicity.
• Compound I-13e exhibited the most potent inhibition, resistance to viral exoribonuclease activity, and suppressed CoV replication.

Conclusions:

• Quinoline and quinazoline derivatives show promise as potential antiviral agents against SARS-CoV-2.
• Compound I-13e is a strong candidate for further development as a therapeutic drug for COVID-19 treatment.