Researchers evaluated the virological characteristics of a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) Omicron lineage named BA.2.86. They conducted epidemic dynamics modeling, experimental studies using current clinically available antivirals, and fusogenicity investigations using hamsters. Their findings revealed that relative to the globally dominant Omicron EG.5.1, the replication number of BA.2.86 is substantially higher.
Encouragingly, four currently available antivirals could effectively treat the novel substrain, and the pathogenicity of the strain (in hamsters) was much lower than that of the parent BA.2 strain. Researchers attribute this reduced pathogenicity to low growth kinetics and decreased reproductive capacity.
Study
In the present study, researchers aimed to investigate the in vitro and in vivo virological features of the BA.2.86 lineage, especially its epidemic potential, RBD affinity, growth kinetics, immune evasive potential, and fusogenicity in hamsters. They further tested the efficacy of current clinically available antivirals in countering the disease.
The epidemic potential of BA.2.86 was evaluated by estimating its relative effective 119 reproduction number (Re) using genome surveillance data derived from six countries with high variant prevalence. A multivariant Bayesian hierarchical multinomial logistic model was used to compute country-specific Re as well as a global extrapolation.
The binding affinity of BA.2.56 was estimated using a yeast display technique. The binding of the S protein RBD of the novel variant to the ACE2 receptor was compared to results from XBB.1.5, which hitherto depicts the highest binding affinity of all known COVID-19 variants. They then tested the infectivity potential of the novel virus using an HIV-1-based pseudovirus. Western blotting of the derived pseudovirus was used to evaluate the cleavage efficiency of the BA.2.86S protein.
Fusogencitiy of BA.2.86 was carried out in vitro using an S 192 protein-mediated membrane fusion assay wherein surface expression levels were estimated in Calu-3/DSP1-7 cells.
Vero cells inoculated with BA.2.86 were used to investigate the growth kinetics of the virus in vitro. Following this, the antiviral sensitivity of the novel variant was measured against nirmatrelvir, ensitrelvir, remdesivir, and EIDD-1931. Finally, in vivo, pathogenicity of the BA.2.86 was tested in hamsters.
Results
The epidemic potential of BA.2.86 was found to be the highest of all known Omicron variants, with the global Re estimated as being 1.07 times higher than EG.5.1. This is noteworthy given the increasing prevalence of BA.2.86, especially in European countries, and suggests that the novel variant will eventually replace EG.5.1 as the globally dominant COVID-19 strain. Binding affinity assays revealed that BA.2.86 had binding comparable to XBB.1.5, and significantly higher than EG.5.1 or its parental BA.2.
Psuedovirus infectivity assays revealed that, in vitro, EG.5.1 outcompetes BA.2.86, with the infectivity of the latter being comparable to its parental BA.2 strain, a viral characteristic also observed in in vitro fusogenicity. However, the cleavage efficiency of BA.2.86 was substantially higher than the ancestral BA.2 strain.
Immune evasion assays revealed that BA.2.86 has significantly more potent immune evasion potential than BA.2 and EG.5.1. However, growth kinetics assays revealed that the growth efficiency of the novel strain was much lower than the current dominant EG.5.1 strain.
All four tested antivirals showed good efficacy against NA.2.86, with Nirmatrelvir showing the best efficacy and EIDD-193 the poorest (yet still positive). In vivo, hamster tests depicted that BA.2.86 infection resulted in body weight loss and reduced pulmonary function. However, these parameters were significantly less potent when compared to EG.5.1 infection. Viral RNA load evaluations revealed similar results (low BA.2.86 load compared to EG.5.1 and even ancestral BA.2), suggesting that BA.2.86 has low in vivo replication efficacy.
Conclusion
The present study evaluated the viral characteristics of the recently discovered BA.2.86 Omicron COVID-19 variant. The multi-analysis study revealed that despite having greater fusogenicity, binding affinity, and epidemic potential than the currently dominant EG.5.1 variant, the novel virus results in less severe infections in hamsters and reduced viral load.
Source:
https://www.news-medical.net/news/20231107/Omicron-variant-BA286-spreads-faster-but-current-antivirals-hold-the-line.aspx