Emily
Editor, Senior Moderator
https://www.nature.com/articles/s41422-022-00617-x#
Xia, S., Chan, J.FW., Wang, L. et al. Peptide-based pan-CoV fusion inhibitors maintain high potency against SARS-CoV-2 Omicron variant. Cell Res 32, 404–406 (2022). https://doi.org/10.1038/s41422-022-00617-x
Dear Editor,
Most recently, a new SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529), was first reported to the World Health Organization (WHO) from South Africa and then quickly spread to many countries,[SUP]1,2[/SUP] posing a serious threat to current vaccine prevention and antibody therapeutic strategies. Several studies have reported that the Omicron variant successfully escapes from neutralizing antibodies elicited by COVID-19 vaccines or from COVID-19 convalescent patients.[SUP]3,4[/SUP] Therefore, the development of potent anti-Omicron agents is urgently needed.
The Omicron variant is documented to have more than 30 mutations in its spike (S) protein, including A67V, del69-70, T95I, G142D, del143-145, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981F (Fig. 1a). These mutations seem to empower the virus to evade neutralizing antibodies against SARS-CoV-2 wild-type (WT) strain. To determine the functional basis for this mutant S, we developed an S-mediated cell–cell fusion assay using 293T cells co-expressing Omicron S protein and EGFP (293T/Omicron/EGFP), as the effector cells, and human ACE2 (hACE2)-expressing Calu-3 cells derived from human lung tissue, or Caco2 cells derived from human intestine tissue, as the target cells. As expected, after coculture of effector and target cells at 37 °C for 24 h, effector cells effectively fused with both Calu-3 cells and Caco2 cells. As shown in Fig. 1b, the fused cells showed larger size and darker fluorescent light than normal cells, and they contained multiple nuclei. Similarly, effector cells bearing Omicron S protein could also fuse with 293T/hACE2 cells, but not 293T cells (Supplementary information, Fig. S1). These results suggest that Omicron variant mutant S protein can interact with hACE2 to mediate viral fusion and infection in human lung and intestine tissues. Previous studies have reported that the fusogenicity found in S protein of SARS-CoV-2 variants favors viral transmissibility and pathogenicity.[SUP]5,6[/SUP] This calls for the development of effective fusion inhibitors against Omicron...
Xia, S., Chan, J.FW., Wang, L. et al. Peptide-based pan-CoV fusion inhibitors maintain high potency against SARS-CoV-2 Omicron variant. Cell Res 32, 404–406 (2022). https://doi.org/10.1038/s41422-022-00617-x
Dear Editor,
Most recently, a new SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529), was first reported to the World Health Organization (WHO) from South Africa and then quickly spread to many countries,[SUP]1,2[/SUP] posing a serious threat to current vaccine prevention and antibody therapeutic strategies. Several studies have reported that the Omicron variant successfully escapes from neutralizing antibodies elicited by COVID-19 vaccines or from COVID-19 convalescent patients.[SUP]3,4[/SUP] Therefore, the development of potent anti-Omicron agents is urgently needed.
The Omicron variant is documented to have more than 30 mutations in its spike (S) protein, including A67V, del69-70, T95I, G142D, del143-145, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981F (Fig. 1a). These mutations seem to empower the virus to evade neutralizing antibodies against SARS-CoV-2 wild-type (WT) strain. To determine the functional basis for this mutant S, we developed an S-mediated cell–cell fusion assay using 293T cells co-expressing Omicron S protein and EGFP (293T/Omicron/EGFP), as the effector cells, and human ACE2 (hACE2)-expressing Calu-3 cells derived from human lung tissue, or Caco2 cells derived from human intestine tissue, as the target cells. As expected, after coculture of effector and target cells at 37 °C for 24 h, effector cells effectively fused with both Calu-3 cells and Caco2 cells. As shown in Fig. 1b, the fused cells showed larger size and darker fluorescent light than normal cells, and they contained multiple nuclei. Similarly, effector cells bearing Omicron S protein could also fuse with 293T/hACE2 cells, but not 293T cells (Supplementary information, Fig. S1). These results suggest that Omicron variant mutant S protein can interact with hACE2 to mediate viral fusion and infection in human lung and intestine tissues. Previous studies have reported that the fusogenicity found in S protein of SARS-CoV-2 variants favors viral transmissibility and pathogenicity.[SUP]5,6[/SUP] This calls for the development of effective fusion inhibitors against Omicron...
