Airborne transmission of SARS-CoV-2 modeled with colossal All-atom molecular dynamics simlulations

The SARS-CoV-2 virus is spread by infected individuals via submicron respiratory aerosol particles emitted during breathing, speaking, or singing. Within the aerosol environment, the virus is protected from direct exposure to the atmosphere, preventing harmful oxidative and radiative damage to the membrane and its integral proteins. It is well-documented that phase and morphology play a significant role in mediating water uptake and atmospheric processing of aerosol particles. However, due to significant instrumental limitations in single-particle aerosol collection and characterization, the molecular mechanisms ensuring viral survival during aerosolization and transmission are still unknown. We take advantage of world-class computing resources to understand the structure and dynamics of colossal (> 1 billion atoms) biomolecular systems, the magnitude of which would otherwise be too great to meaningfully simulate with standard supercomputing facilities. We describe the application of all-atom molecular dynamics simulations to investigate the behavior and dynamics of the novel SARS-CoV-2 virion within a respiratory aerosol mimic. A spherical ERGIC-like bilayer was constructed and carefully equilibrated. The delta variant spike (S), membrane (M), and envelope (E) proteins were placed into the bilayer in accordance with experimental observations. The equilibrated virion was then placed into a 1 billion-atom respiratory aerosol mimic to investigate the role of pulmonary mucus, lipids, proteins, and cations on airborne virion transfer and stabilization. Pulmonary mucus, a likely component of respiratory aerosols, is known to undergo gel-like phase transitions in the deep lung with increasing acidity and calcium coordination. We hypothesize that, when aerosolized, calcium similarly facilitates the coordination of mucus to the S proteins and their glycans, reducing water loss and protecting the viral membrane from atmospheric deactivation. Our simulations reveal the phase and morphology of viral-laden respiratory aerosols, reframing the way we consider the transmission of airborne pathogens for both drug discovery and public health mitigation decisions.