Bioenergetics Modeling in Viral Replication and Clearance Applied to SARS-CoV-2

Abstract

Kinetic and thermodynamic parameters for viral replication and depletion were given less attention in the literature. The activation energies for viral replication (e.g., 135—167 kJ/mol), clearance (119.1—137.3 kJ/mol), and cell death (e.g., 119.5—137.8 kJ/mol) were lower earlier on than later. The values of dimensionless equilibrium constant () for viral replication (0.000045-0.003681) in Nef-positive HSC-F cells were greater than for Nef-negative HSC-F cells (0.000003-0.000353); those for viral depletion were generally higher (0.000004-0.004539). The magnitude of  values diminished with time. The free energies (s) for viral replication and depletion in the cells were greater for negative (20.50-32.990 kJ/mol) than for positive cells (14.450-25.810 kJ/mol); the activation energies () for replication (116.7-135.1 kJ/mol) and cell death (125.5-137.8 kJ/mol) for negative cells were greater than those (117.8-129.2 kJ/mol & 119.5-130.9 kJ/mol, respectively) for positive cells. The free energies of activation () for viral replication and cell death for positive and negative cells were 103.35 and 105.08 kJ/mol and 102.30 and 104.99 kJ/mol, respectively; the value of ‘ for viral depletion was 105.234 kJ/mol. The for virus depletion and replication, was calculated using data reported for Nef—positive and —negative HSC—F cells in the literature. Applying the result in this study to SARS-CoV-2, calls for weekly evaluation of therapeutic interventions. Since dimensionless equilibrium constant values for viral replication, depletion, and concomitant cell death are higher earlier on than later, it is diagnostically and therapeutically wise to adopt early interventions. These should lower the dimensionless equilibrium constant values and heighten the free energy (increasing the positive magnitude) and activation energy of viral replication and cell death with appropriate medications. The same parameters for viral depletion or clearance are expected to be heightened, more feasible with lower energy barriers. Future studies, in vivo and in vitro, calls for weekly evaluation possibly at different temperatures.