Molecular modeling of the methylene blue interaction with the SARS-CoV-2 coronavirus viroporin

Viroporins are small membrane proteins of enveloped viruses. They play an important role both in the life cycle of the virus and in the development of disease pathogenesis. In this regard, inhibition of viroporins is considered a promising strategy in the treatment of many diseases caused by enveloped viruses, such as coronavirus, herpes virus, human immunodeficiency virus, Ebola virus and many others. An important step in the search for highly effective inhibitors of such channels is the study of the interaction of potential antiviral drugs with the amino acid residues of the viroporin channel. In turn, methylene blue is a well-known effective antiviral agent and is widely used in medical practice. In this work, we carried out molecular dynamic calculations of the interaction of methylene blue with the viroporin channel of the SARS-CoV-2 coronavirus using the umbrella sampling method. Analysis of the contacts formed between the methylene blue molecule and the amino acid residues of viroporin showed that the key role in binding is played by non-covalent stacking interactions between the system of aromatic rings of methylene blue and the phenylalanine residues located in the center of the viroporin channel. The results obtained bring us closer to understanding the mechanisms of the antiviral action of methylene blue. Conducting such computational experiments seems to be an effective approach in the search for viroporin inhibitors.