Lipopeptides against COVID-19 RNA-dependent RNA polymerase using molecular docking

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2.
• Despite existing treatments, the virus's infectivity and mutation rate necessitate novel therapeutic strategies.

Purpose of the Study:

• To investigate the potential of lipopeptides as antiviral agents against SARS-CoV-2.
• To predict the binding affinity of various lipopeptides to the viral RNA-dependent RNA polymerase (nsp12).

Main Methods:

• Molecular docking simulations were employed to assess lipopeptide binding to SARS-CoV-2 nsp12.
• Protein-ligand interaction analysis was performed to understand binding mechanisms.

Main Results:

• Seven lipopeptides demonstrated high binding affinity to nsp12, comparable to or exceeding that of remdesivir.
• Ferrocin A-iron complex (FAC) exhibited the strongest binding to nsp12, with a free energy release of 9.1 kcal mol⁻¹.
• FAC formed multiple interactions, including hydrogen bonds and salt bridges, with conserved amino acids in nsp12.

Conclusions:

• The studied lipopeptides, particularly FAC, are promising candidates for developing new anti-SARS-CoV-2 drugs.
• Targeting the nsp12 enzyme with these lipopeptides offers a potential therapeutic avenue for COVID-19 treatment.