Modeling the interaction of C60 fullerene with SARS-CoV-2 protein targets
Abstract
Background: The discovery of effective therapeutics against the dangerous disease caused by SARS-CoV-2 is an important direction of biomedical research. Molecular docking and molecular dynamics methods are key tools of modern pharmaceutical science, providing rapid search and optimization of antiviral compounds, allowing to predict their effectiveness and adapt therapy to new strains of SARS-CoV-2. Fullerene C60 attracts considerable attention as a promising nanomaterial in the fight against SARS-CoV-2 due to its ability to form stable complexes with key viral proteins, such as the main protease (3CLpro) and RNA-dependent RNA polymerase (RdRp). Molecular modeling and biophysical studies have shown that C60 can penetrate the lipid envelope of the virus and block the functional activity of its proteins, which opens up opportunities for the creation of new antiviral drugs. Given the constant mutations of SARS-CoV-2 and the limitations of existing therapeutics, the study of C60 fullerene as a potential inhibitor is a relevant direction of nanotechnology for the development of innovative strategies for the treatment of COVID-19.
Aim of the work was to assess in silico the ability of C60 fullerene to interact with the protein targets 3CLpro (3-Chymotrypsin-Like protease) and RdRp (RNA-dependent RNA polymerase) of the SARS-CoV-2 coronavirus and, thus, to specifically block them, inhibiting the functional activity of SARS-CoV-2.
Methods: Structural data of the 3CLpro and RdRp proteins of the SARS-CoV-2 coronavirus were obtained from the Protein Data Bank, and the geometry of C60 fullerene was generated using the online server SwissParam. Interactions between С60 fullerene and the studied proteins were modeled using the system molecular docking algorithm (sdock+). Potential binding sites were determined using the Caver software package. Molecular dynamics calculations were performed in the Gromacs 2020 software environment. Energy minimization of potential C60 fullerene — protein complexes was performed using the g_mmpbsa software.
Results: Putative mechanism of binding of C60 fullerene to the protein targets 3CLpro and RdRp of the SARS-CoV-2 coronavirus was established. Molecular docking and molecular dynamics data demonstrate that C60 fullerene forms stable complexes with these proteins, which can lead to inhibition of their functional activity.
Conclusions: It is shown that C60 fullerene is able to form stable complexes with the 3CLpro and RdRp proteins of SARS-CoV-2, which potentially reduces their activity and, accordingly, can affect the overall activity of the coronavirus.
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References
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