SARS-CoV-2 Spreads through Cell-to-Cell Transmission.

bioRxiv : the preprint server for biology (2021-06-09)
Cong Zeng, John P Evans, Tiffany King, Yi-Min Zheng, Eugene M Oltz, Sean P J Whelan, Linda Saif, Mark E Peeples, Shan-Lu Liu

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While ACE2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the variants of concern (VOC) B.1.1.7 and B.1.351 have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccine sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.

Product Number
Product Description

Leupeptin, microbial, ≥90% (HPLC)
Methyl cellulose, viscosity: 4,000 cP
Cathepsin L Inhibitor III - Calbiochem, The Cathepsin L Inhibitor III controls the biological activity of Cathepsin L. This small molecule/inhibitor is primarily used for Protease Inhibitors applications.
EST - CAS 88321-09-9 - Calbiochem, A cell-permeable, irreversible inhibitor of cysteine proteases.
Crystal Violet, certified by the Biological Stain Commission
Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)
CA-074 Me - Calbiochem, CA-074 Me, CAS 147859-80-1, is a cell-permeable analog of CA-074 that acts as an irreversible inhibitor of intracellular cathepsin B.