A seventh, SARS-CoV-2, emerged in the winter of 2019 from Wuhan, China. Until late 2019, only six coronaviruses were known to infect humans: HCoV-229E, HCoV-OC43, SARS-CoV (SARS-CoV-1), HCoV-NL63, CoV-HKU1, and MERS-CoV. These results show S G614 is more stable than S D614, consistent with epidemiological data suggesting that viruses with S G614 transmit more efficiently. However, S G614 did not bind ACE2 more efficiently than S D614, and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma. Similar results were obtained using the virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. This greater infectivity was correlated with less S1 shedding and greater incorporation of the S protein into the pseudovirion. We observed that retroviruses pseudotyped with S G614 infected ACE2- expressing cells markedly more efficiently than those with S D614. We therefore compared the functional properties of the S proteins with aspartic acid (S D614) and glycine (S G614) at residue 614. Lizhou Zhang 1#, Cody B Jackson 1#, Huihui Mou 1#, Amrita Ojha 1, Erumbi S Rangarajan 2, Tina Izard 2, Michael Farzan 1*, Hyeryun Choe 1* 1Department of Immunology and Microbial Science, The Scripps Research Institute, Jupiter, FL 33458, USA 2Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, Florida 33458 #contributed equally *Correspondence: coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission.

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