SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity

SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (S-G614) with the original (S-D614). We report here pseudoviruses carrying S-G614 enter ACE2-expressing cells more efficiently than those with S-D614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. SARS-CoV-2 variants with spike (S)-protein D614G mutations currently predominate globally. Here, Zhang et al. hypothesize that D614G variant may increase infectivity by increasing S protein abundance on the virion since pseudoviruses carrying S-G614 incorporate higher amounts of S protein and enter cells more efficiently than those carrying S-D614.