Assessing the interaction between hemoglobin and the receptor binding domain of SARS-CoV-2 spike protein through MARTINI coarse-grained molecular dynamics

Abstract

The emergence of different coronavirus-related diseases in the 2000's (SARS, MERS, and Covid-19) warrants the need of a complete understanding of the pathological, biological, and biochemical behavior of this class of pathogens. Great attention has been paid to the SARS-CoV-2 Spike protein, and its interaction with the human ACE2 has been thoroughly investigated. Recent findings suggested that the SARS-CoV-2 components may interact with different human proteins, and hemoglobin has very recently been demonstrated as a potential target for the Spike protein. Here we have investigated the interaction between either adult or fetal hemoglobin and the receptor binding domain of the Spike protein at molecular level through advanced molecular dynamics techniques and proposed rational binding modes and energy estimations. Our results agree with biochemical data previously reported in literature. We also demonstrated that co-incubation of pulmonary epithelial cells with hemoglobin strongly reduces the pro-inflammatory effects exerted by the concomitant administration of Spike protein.