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Focosi, D.

Publications and source records attributed to Focosi, D..

3 recordsLinked to original sources

ConvMut: A Web tool to analyze viral convergent mutations along phylogenies

Convergent evolution in protein antigens is common across pathogens and has also been documented in SARS-CoV-2 (hCoV-19); the most likely reason is the need to evade the selective pressure exerted by previous infection- or vaccine-elicited immunity. There is a pressing need for tools that allow automated analysis of convergent mutations. In response to this need, we developed ConvMut, a tool to analyze genetic sequence data to identify patterns of recurrent mutations in SARS-CoV-2 evolution. To this end, we exploited the granular phylogenetic tree representation developed by PANGO, allowing us to observe what we call deltas, i.e., groups of mutations that are acquired on top of the immediately upstream tree nodes. Deltas comprise amino acid substitutions, insertions, and deletions. ConvMut can perform individual protein analysis to identify the most common single mutations acquired independently in a given subtree (starting from a user-selected root). Such mutations are represented in a barplot that can be sorted by frequency or position, and filtered by region of interest. Lineages are then gathered into clusters according to their sets of shared mutations. Finally, an interactive graph orders the evolutionary steps of clusters, details the acquired amino acid changes for each sublineage, and allows us to trace the evolutionary path until a selected lineage. Other unique tools are paired with the main functionality of ConvMut to support a complete analysis, such as a frequency analysis for a given nucleotide or amino acid changes at a given residue across a selected phylogenetic subtree. ConvMut will facilitate the design of antiviral anti-Spike monoclonal antibodies and Spike-based vaccines with longer-lasting efficacy, minimizing development and marketing failures.

bioinformatics↗

Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves.

The first 2 years of the COVID-19 pandemic were mainly characterized by convergent evolution of mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 across different variants of concern (Alpha, Beta, Gamma, and Delta). Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494. Mutations at these residues have become increasingly prevalent during Summer and Autumn 2022, with combinations showing increased fitness. The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity. Such accelerated evolution has caused failure of all anti-Spike monoclonal antibodies, including bebtelovimab and cilgavimab. While we are learning how fast coronaviruses can mutate and recombine, we should reconsider opportunities for economically sustainable escape-proof combination therapies, and refocus antibody-mediated therapeutic efforts on polyclonal preparations that are less likely to allow for viral immune escape.

microbiology↗

Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ1.1 and XBB.

ObjectivesRecent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity. MethodsHere we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination. ResultsMore than 90% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, and BF.7 with 100% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50% neutralizing titers (GM (GMT50) were 314, 78 and 204 for BQ.1.1, XBB.1 and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naive subjects who also recently within 6 months received at least a third vaccine dose had about half of the GM (GMT50) for all viral variants. ConclusionsBoosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.

microbiology↗