Molecular In-Depth on the Epidemiological Expansion of SARS-CoV-2 XBB.1.5.

Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10-4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant.

Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages.

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

Genome-based survey of the SARS-CoV-2 BF.7 variant from Asia.

The SARS-CoV-2 BF.7 variant represents one of the most recent subvariant under monitoring. At the beginning of the 2023 it caused several concerns especially in Asia because of a resurge in COVID-19 cases. Here we perform a genome-based integrative approach on SARS-CoV-2 BF.7 to shed light on this emerging lineage and produce some consideration on its real dangerousness. Both genetic and structural data suggest that this new variant currently does not show evidence of an high expansion capability. It is very common in Asia, but it appears less virulent than other Omicron variants as proved by its relatively low evolutionary rate (5.62 × 10-4 subs/sites/years). The last plateau has been reached around December 14, 2022 and then the genetic variability, and thus the viral population size, no longer increased. As already seen for several previous variants, the features that may be theoretically related to advantages are due to genetic drift that allows to the virus a constant adaptability to the host, but is not strictly connected to a fitness advantage. These results have further pointed that the genome-based monitoring must continue uninterruptedly to be prepared and well documented on the real situation.

Genetic and Structural Data on the SARS-CoV-2 Omicron BQ.1 Variant Reveal Its Low Potential for Epidemiological Expansion.

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 has some additional spike mutations in some key antigenic sites, which confer further immune escape ability over other circulating lineages. In such a context, here, we perform a genome-based survey aimed at obtaining a complete-as-possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggest that BQ.1 represents an evolutionary blind background, lacking the rapid diversification that is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10-4 and 7 × 10-4 subs/site/year, respectively), which has been circulating for several months. The Bayesian Skyline Plot reconstruction indicates a low level of genetic variability, suggesting that the peak was reached around 3 September 2022. Concerning the affinity for ACE2, structure analyses (also performed by comparing the properties of BQ.1 and BA.5 RBD) indicate that the impact of the BQ.1 mutations may be modest. Likewise, immunoinformatic analyses showed moderate differences between the BQ.1 and BA5 potential B-cell epitopes. In conclusion, genetic and structural analyses on SARS-CoV-2 BQ.1 suggest no evidence of a particularly dangerous or high expansion capability. Genome-based monitoring must continue uninterrupted for a better understanding of its descendants and all other lineages.

Update on the Phylodynamics of SADS-CoV.

Coronaviruses are known to be harmful and heterogeneous viruses, able to infect a large number of hosts. Among them, SADS-CoV (Swine Acute Diarrhea Syndrome Coronavirus), also known as PEAV (Porcine Enteric Alphacoronavirus), or SeA-CoV (Swine Enteric Alphacoronavirus), is the most recent Alphacoronavirus discovered, and caused several outbreaks reported in Chinese swine herds between late 2016 and 2019. We performed an upgraded phylodinamic reconstruction of SADS-CoV based on all whole genomes available on 21 June 2021. Results showed a very close relationship between SADS-CoV and HKU2-like CoV, which may represent the evolutionary intermediate step towards the present SADS-CoV. The direct progenitor of SADS-CoV is so far unknown and, although it is well known that horseshoe bats are reservoirs for Rhinolophus bat coronavirus HKU2-like (HKU2-like CoVs), the transmission path from bats to pigs is still unclear. The discrepancies in the phylogenetic position of rodent CoV, when different molecular markers were considered, corroborate the recombination hypothesis, suggesting that wild rats, which are frequent in farms, may have played a key role. The failure of the attempt at molecular dating, due to the lack of a clock signal, also corroborates the occurrence of a recombination event hypothesis. Zoonotic infections originating in wildlife can easily become a significant threat for human health. In such a context, due to the high recombination and cross-species capabilities of Coronavirus, SADS-CoV represents a possible high-risk pathogen for humans which needs a constant molecular monitoring.