In Silico Analysis of C60 Fullerene Interaction with TMPRSS2: Toward Novel COVID-19 Prevention Approaches.

The recent global spread of the SARS-CoV-2 pathogen, which causes COVID-19, and its rapid mutation, requires the fast development of effective preventive and treatment measures. According to WHO reports, over 778 million confirmed cases of COVID-19 have been reported, including approximately 7 million deaths. The androgen-regulated cell-surface serine protease TMPRSS2 interacts with the SARS-CoV-2 spike protein. Therefore, directly inhibiting TMPRSS2 will negatively impact the activation of coronaviruses and, consequently, disease progression. That is why TMPRSS2 is a very important target in current drug discovery. On the other hand, it is known that C60 fullerene (a nearly spherical molecule consisting of 60 carbon atoms) exhibits activity against various protein targets. Here, for the first time, the potential binding of C60 fullerene with TMPRSS2 was investigated using different computer simulation methods, including p2Rank, PCA, gmx_MMPBSA analysis, molecular docking, and molecular dynamics simulations. As a result, four potential binding pockets on the TMPRSS2 surface that could interact with C60 fullerene were identified. Among all "C60 fullerene-TMPRSS2" complexes, one was selected as the most promising binding site based on the results of computational modeling evaluations. This opens up the prospect of creating new anticoronavirus drugs based on these carbon nanoparticles.