Introduction: The coronavirus is the cause of the infectious pneumonia disease COVID 19, which since 2019 the World Health Organization (WHO) has declared as a global pandemic, which is still spreading. Spike protein in SARS COV2 virus is an important factor in pathogenesis, which includes two regions S1 and S2. The S1 subunit has the role of binding to the host receptor and the S2 subunit has the role of membrane fusion between the host cell and the virus. The S2 region is a more protected region than S1, so the probability of mutation in it is reduced. A region in S2 called FP (Fusion Protein) plays a vital role in membrane fusion, which starts the process of membrane fusion by entering the lipid bilayer of the host and disrupting the membrane structure.
In this research, with modern bioinformatics methods, inhibitor design for the FP region has been done in order to prevent the occurrence of membrane fusion and disrupt the entry and proliferation of this virus.
Methods: The region related to FP in PDB:6VXX was considered from amino acid 788 to 806. Then amino acids with high interaction were determined for this sequence with the assumption that they can be complementary sequences of the intended sequence. These sequences were modeled using RaptorX, Swissmodel, and Phyer2 servers, and the accuracy of the built models was evaluated using the Procheck server. The binding energy of the designed models was calculated via the molecular docking method using the Haddock.version 2.4 server.
Results: The region related to FP in PDB:6VXX was considered from amino acid 788 to 806. Then amino acids with high interaction were determined for this sequence with the assumption that they can be complementary sequences of the intended sequence. These sequences were modeled using RaptorX, Swissmodel, and Phyer2 servers, and the accuracy of the built models was evaluated using the Procheck server. The binding energy of the designed models was calculated via the molecular docking method using the Haddock.version 2.4 server.
Conclusion: The results obtained from molecular docking showed that the designed models have a high tendency to connect to the FP region and the binding energy values calculated for the top 5 models are -120, -96, -93, -90.6 and -90.5 kcal/mol, respectively.
As a result, these models can be used to inhibit the spike protein from the FP region and prevent the virus from entering and infecting the host cell. These types of inhibitors can be useful and effective in making vaccines or antiviral drugs.