tetano
Editor, Senior Moderator
Cell Rep
. 2025 Aug 13;44(8):116135.
doi: 10.1016/j.celrep.2025.116135. Online ahead of print. Signatures of omicron-like adaptation in early SARS-CoV-2 variants and chronic infection
Mark Tsz Kin Cheng[SUP] 1 [/SUP], Mazharul Altaf[SUP] 1 [/SUP], Jesu Castin[SUP] 2 [/SUP], Ann-Kathrin Reuschl[SUP] 3 [/SUP], Benjamin L Sievers[SUP] 1 [/SUP], Kimia Kamelian[SUP] 1 [/SUP], Dejan Mesner[SUP] 3 [/SUP], Rebecca B Morse[SUP] 1 [/SUP], Adam Abdullahi[SUP] 1 [/SUP], Bo Meng[SUP] 1 [/SUP], Kata Csiba[SUP] 1 [/SUP]; Cambridge NIHR Bioresource; Steven A Kemp[SUP] 1 [/SUP], Darren P Martin[SUP] 4 [/SUP], Clare Jolly[SUP] 3 [/SUP], Christopher Ruis[SUP] 5 [/SUP], Lipi Thukral[SUP] 6 [/SUP], Ravindra K Gupta[SUP] 7 [/SUP]
Affiliations
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a source of new variants and can provide insight into evolutionary trajectories. Here, we observe upper airway-specific evolution of SARS-CoV-2, demonstrating a fusion peptide (FP) domain mutation (S
812S) adjacent to the S2' cleavage site that emerged during a chronic infection. Indeed, this mutation had emerged previously and been transmitted in a delta variant lineage. P812S in a spike-pseudotyped virus did not impact entry efficiency. However, cleavage at S1/S2 was reduced, and molecular dynamics simulation demonstrated altered S1/S2 loop conformations. Consistent with impaired S1/S2 cleavage, and reminiscent of Omicron BA.1, cell-cell fusogenicity was severely impaired by P812S. P812S conferred evasion of a FP-targeting monoclonal antibody, consistent with FP-region structural rearrangements. Finally, P812S-bearing viruses showed evasion of polyclonal neutralizing antibodies in sera from vaccinated individuals at 32C. These data shed light on the balance between SARS-CoV-2 upper airway adaptation/immune evasion, syncytium formation, and pathogenic potential.
Keywords: COVID-19; CP: Microbiology; SARS CoV-2; evolution; fusion; immunocompromised; infectivity; omicron; serology.
. 2025 Aug 13;44(8):116135.
doi: 10.1016/j.celrep.2025.116135. Online ahead of print. Signatures of omicron-like adaptation in early SARS-CoV-2 variants and chronic infection
Mark Tsz Kin Cheng[SUP] 1 [/SUP], Mazharul Altaf[SUP] 1 [/SUP], Jesu Castin[SUP] 2 [/SUP], Ann-Kathrin Reuschl[SUP] 3 [/SUP], Benjamin L Sievers[SUP] 1 [/SUP], Kimia Kamelian[SUP] 1 [/SUP], Dejan Mesner[SUP] 3 [/SUP], Rebecca B Morse[SUP] 1 [/SUP], Adam Abdullahi[SUP] 1 [/SUP], Bo Meng[SUP] 1 [/SUP], Kata Csiba[SUP] 1 [/SUP]; Cambridge NIHR Bioresource; Steven A Kemp[SUP] 1 [/SUP], Darren P Martin[SUP] 4 [/SUP], Clare Jolly[SUP] 3 [/SUP], Christopher Ruis[SUP] 5 [/SUP], Lipi Thukral[SUP] 6 [/SUP], Ravindra K Gupta[SUP] 7 [/SUP]
Affiliations
- PMID: 40811064
- DOI: 10.1016/j.celrep.2025.116135
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a source of new variants and can provide insight into evolutionary trajectories. Here, we observe upper airway-specific evolution of SARS-CoV-2, demonstrating a fusion peptide (FP) domain mutation (S
812S) adjacent to the S2' cleavage site that emerged during a chronic infection. Indeed, this mutation had emerged previously and been transmitted in a delta variant lineage. P812S in a spike-pseudotyped virus did not impact entry efficiency. However, cleavage at S1/S2 was reduced, and molecular dynamics simulation demonstrated altered S1/S2 loop conformations. Consistent with impaired S1/S2 cleavage, and reminiscent of Omicron BA.1, cell-cell fusogenicity was severely impaired by P812S. P812S conferred evasion of a FP-targeting monoclonal antibody, consistent with FP-region structural rearrangements. Finally, P812S-bearing viruses showed evasion of polyclonal neutralizing antibodies in sera from vaccinated individuals at 32C. These data shed light on the balance between SARS-CoV-2 upper airway adaptation/immune evasion, syncytium formation, and pathogenic potential.Keywords: COVID-19; CP: Microbiology; SARS CoV-2; evolution; fusion; immunocompromised; infectivity; omicron; serology.