Phylogenetic and computational methods reveal that at least two seasonal coronaviruses are evolving adaptively in the region of the viral spike protein exposed to the human humoral immune system.

The HCoV-229E coronavirus S-protein accommodates extensive mutational change and possesses hydrophilic subunit interfaces in the S2 region, features that provide new insights into immune evasion, cross-species transmission and membrane fusion.

Non-neutralizing antibodies to the SARS-CoV-2 spike protein’s S2 domain that also recognize widely circulating endemic coronavirus strains are rapidly boosted by natural infection but not vaccination with stabilized spike-based vaccines.

Cell culture adaptation of SARS-CoV-2 is prevented on human airway cells with an active serine protease-mediated entry pathway, allowing the production of genetically stable virus stocks for laboratory experiments.

SARS-CoV-2 infection and vaccination elicit antibodies that cross-react with other human coronavirus spike proteins, indicating the spike S2 subdomain as a potential target strategy to develop a pan-coronavirus vaccine.

Viruses, including SARS-CoV-2, retain infectivity longer at low temperatures and extreme relative humidities because these conditions slow down the chemical reactions that inactivate those viruses.

The molecular microenvironment of coronaviral replicase complexes provides functional and spatial links between conserved cellular processes and viral RNA synthesis, and highlights potential targets for the development of novel antivirals.