Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.

| S-EPMC9444898 | biostudies-literature

Genomic architecture and evolutionary relationship of BA.2.75: A Centaurus subvariant of Omicron SARS-CoV-2.

Project description:In this study, we explored the genomic architecture and phylogenomic relationship of BA.2.75, a subvariant of Omicron SARS-CoV-2. A set of 1468 whole-genome sequences of BA.2.75, submitted by 28 countries worldwide were retrieved from GISAID and used for finding genomic mutations. Moreover, the phylogenetic analysis of BA.2.75 was performed by using 2948 whole-genome sequences of all sub-variants of Omicron along with the Delta variant of SAS-CoV-2. We detected 1885 mutations, which were further grouped into 1025 missense mutations, 740 silent mutations, 72 mutations in non-coding regions, 16 in-frame deletions, 02 in-frame insertions, 8 frameshift deletions, 8 frameshift insertions and 14 stop-gained variants. Additionally, we also found 11 characteristic mutations having a prevalence of 81-99% and were not observed in any of the previously reported variant of SARS-CoV-2. Out of these mutations K147E, W152R, F157L, E210V, V213G, G339H were found in the NTD, and G446S & N460K in the RBD region of the Spike protein, whereas S403L and T11A were present in the NSP3, and E protein respectively. The phylogenetic relationship of this variant revealed that BA.2.75 is descended from the Omicron sub-variant BA.5. This evolutionary relationship suggests that the surge of BA.5 infections can reduce the severity of the infections accredited to BA.2.75. These findings would also improve our knowledge and understanding that how genetic similarities in different variants of SARS-CoV-2 can prime the immune system to fight off the infection caused by one subvariant, after defeating the other.

| S-EPMC10208454 | biostudies-literature

An imported human case with the SARS-CoV-2 Omicron subvariant BA.2.75 in Yunnan Province, China.

Project description:The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021. It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike (S) protein than the previously circulating variants of concern (VOCs). Notably, on 15 July 2022, we monitored the first VOC / Omicron subvariant BA.2.75 in China from an imported case. Moreover, nowadays, this subvariant still is predominant in India. It has nine additional mutations in the S protein compared to BA.2, three of which (W152R, G446S, and R493Q reversion) might contribute to higher transmissibility and immune escape. This subvariant could cause wider spread and pose a threat to the global situation. Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.

| S-EPMC9613801 | biostudies-literature

Omicron subvariant BA.5 efficiently infects lung cells.

Project description:The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.

| S-EPMC10262933 | biostudies-literature

Evasion of neutralising antibodies by omicron sublineage BA.2.75.

Project description: Not available

| S-EPMC9436366 | biostudies-literature

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates.

Project description:The prevalence of the Omicron subvariant BA.2.75 rapidly increased in India and Nepal during the summer of 2022, and spread globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs is higher than that of BA.2 and BA.5. Of note, BA.2.75 causes focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which is not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicates better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 in a hamster model and should be closely monitored.

| S-EPMC10035475 | biostudies-literature

Comparative neutralisation profile of SARS-CoV-2 omicron subvariants BA.2.75 and BA.5.

Project description: Not available

| S-EPMC9365316 | biostudies-literature