Fever temperatures modulate intraprotein dynamics and enhance the binding affinity between monoclonal antibodies and the spike protein from SARS-CoV-2.

Fever is a typical symptom of most infectious diseases. While prolonged fever may be clinically undesirable, mild reversible fever (<39℃, 312 K) can potentiate the immune responses against pathogens. Here, using molecular dynamics and free energy calculations, we investigated the effect of febrile temperatures (38℃ to 40℃, 311 K to 313 K) on the immune complexes formed by the SARS-CoV-2 spike protein with two neutralizing monoclonal antibodies. In analyzing the conformational dynamics of the interactions between the antibodies and the spike protein under different thermal conditions, we found that, at mild fever temperatures (311-312 K), the binding affinities of the two antibodies improve when compared to the physiological body temperature (37℃, 310 K). Furthermore, only at 312 K, antibodies exert distinct mechanical effects on the receptor binding domains of the spike protein that may hinder SARS-CoV-2 infectivity. Enhanced antibody binding affinity may thus be obtained using appropriate temperature conditions.