Insight into the LFA-1/SARS-CoV-2 Orf7a Complex by Protein-Protein Docking, Molecular Dynamics, and MM-GBSA Calculations.

Alberto Ongaro, Erika Oselladore, Maurizio Memo, Giovanni Ribaudo, Alessandra Gianoncelli

Journal of chemical information and modeling 2021 Jun 28

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In the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome, open reading frames (ORFs) encode for viral accessory proteins. Among these, Orf7a structurally resembles the members of the immunoglobulin (Ig) superfamily and intracellular adhesion molecules (ICAMs), in particular. ICAMs are involved in integrin binding through lymphocyte function-associated antigen 1 (LFA-1). Based on such considerations and on previous findings on SARS-CoV, it has been postulated that the formation of the LFA-1/Orf7a complex could contribute to SARS-CoV-2 infectivity and pathogenicity. With the current work, we aim at providing insight into this macromolecular assembly, taking advantage of the recently reported SARS-CoV-2 Orf7a structure. Protein-protein docking, molecular dynamics (MD) simulations, and a Molecular Mechanical-Generalized Born Surface Area (MM-GBSA)-based stage were enrolled to provide refined models.

Citation

Alberto Ongaro, Erika Oselladore, Maurizio Memo, Giovanni Ribaudo, Alessandra Gianoncelli. Insight into the LFA-1/SARS-CoV-2 Orf7a Complex by Protein-Protein Docking, Molecular Dynamics, and MM-GBSA Calculations. Journal of chemical information and modeling. 2021 Jun 28;61(6):2780-2787