Computational Analysis of CD46 Protein Interaction with SARS-CoV-2 Structural Proteins: Elucidating a Putative Viral Entry Mechanism into Human Cells
Pavel Vassiliev,
Evgenii Gusev,
Maria Komelkova,
Andrey Kochetkov,
Maria Dobrynina,
Alexey Sarapultsev
Affiliations
Pavel Vassiliev
Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs, Research Center for Innovative Medicines, Volgograd State Medical University, 39 Novorossiyskaya Street, Volgograd 400087, Russia
Evgenii Gusev
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, Yekaterinburg 620049, Russia
Maria Komelkova
Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, Chelyabinsk 454080, Russia
Andrey Kochetkov
Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs, Research Center for Innovative Medicines, Volgograd State Medical University, 39 Novorossiyskaya Street, Volgograd 400087, Russia
Maria Dobrynina
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, Yekaterinburg 620049, Russia
Alexey Sarapultsev
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, Yekaterinburg 620049, Russia
This study examines an unexplored aspect of SARS-CoV-2 entry into host cells, which is widely understood to occur via the viral spike (S) protein’s interaction with human ACE2-associated proteins. While vaccines and inhibitors targeting this mechanism are in use, they may not offer complete protection against reinfection. Hence, we investigate putative receptors and their cofactors. Specifically, we propose CD46, a human membrane cofactor protein, as a potential putative receptor and explore its role in cellular invasion, acting possibly as a cofactor with other viral structural proteins. Employing computational techniques, we created full-size 3D models of human CD46 and four key SARS-CoV-2 structural proteins—EP, MP, NP, and SP. We further developed 3D models of CD46 complexes interacting with these proteins. The primary aim is to pinpoint the likely interaction domains between CD46 and these structural proteins to facilitate the identification of molecules that can block these interactions, thus offering a foundation for novel pharmacological treatments for SARS-CoV-2 infection.
