Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020–February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay’s capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.

Temporal Increase in Neutralization Potency of SARS-CoV-2 Antibodies and Reduced Viral Variant Escape after Sputnik V Vaccination

ABSTRACTRecent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we observed a similar process after Sputnik V vaccination. We examined the longitudinal antibody responses and viral neutralizing capacity to variants of concern (VOCs: Alpha, Beta, Gamma, and Delta) and a broadly spread variant of interest (VOI: Lambda) in volunteers up to 6 months after receiving the Sputnik V vaccine in Argentina. A collection of 1,800 serum samples obtained between January and August 2021 was used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing potency to the first-wave linages of SARS-CoV-2 and VOC increases within four months of vaccination, suggesting that antibody maturation occurs. This increase was more evident for the Beta and Gamma variants, which showed the highest propensity for neutralization escape. Our observations suggest that protection increases over the six months following vaccination as a consequence of antibody maturation, resulting in improved potency of antibodies to viral escape mutations.

Cutting epitopes to survive: the case of lambda variant

This manuscript concisely reports an in-silico study on the potential impact of the Spike protein mutations on immuno-escape ability of SARS-CoV-2 lambda variant. Biophysical and bioinformatics data suggest that a combination of shortening immunogenic epitope loops and generation of potential N-glycosylation sites may be a viable adaptation strategy potentially allowing this emerging viral variant escaping host immunity.

Structural and energetic profiling of SARS-CoV-2 antibody recognition and the impact of circulating variants

The SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including B.1.1.7, P1, and B.1.351, some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.

Viral Variants and Vaccinations: If We Can Change the COVID-19 Vaccine… Should We?

As we close in on one year since the COVID-19 pandemic began, hope has been placed on bringing the virus under control through mass administration of recently developed vaccines. Unfortunately, newly emerged, fast-spreading strains of COVID-19 threaten to undermine progress by interfering with vaccine efficacy. While a long-term solution to this challenge would be to develop vaccines that simultaneously target multiple different COVID-19 variants, this approach faces both developmental and regulatory hurdles. A simpler option would be to switch the target of the current vaccine to better match the newest viral variant. I use a stochastic simulation to determine when it is better to target a newly emerged viral variant and when it is better to target the dominant but potentially less transmissible strain. My simulation results suggest that it is almost always better to target the faster spreading strain, even when the initial prevalence of this variant is much lower. In scenarios where targeting the slower spreading variant is best, all vaccination strategies perform relatively well, meaning that the choice of vaccination strategy has a small effect on public health outcomes. In scenarios where targeting the faster spreading variant is best, use of vaccines against the faster spreading viral variant can save many lives. My results provide ‘rule of thumb’ guidance for those making critical decisions about vaccine formulation over the coming months.

Introduction into the Marseille geographical area of a mild SARS-CoV-2 variant originating from sub-Saharan Africa

ABSTRACTBACKGROUNDIn Marseille, France, the COVID-19 incidence evolved unusually with several successive epidemic episodes. The second outbreak started in July, was associated with North Africa, and involved travelers and an outbreak on passenger ships. This suggested the involvement of a new viral variant.METHODSWe sequenced the genomes from 916 SARS-CoV-2 strains from COVID-19 patients in our institute. The patients’ demographic and clinical features were compared according to the infecting viral variant.RESULTSFrom June 26th to August 14th, we identified a new viral variant (Marseille-1). Based on genome sequences (n=89) or specific qPCR (n=53), 142 patients infected with this variant were detected. It is characterized by a combination of 10 mutations located in the nsp2, nsp3, nsp12, S, ORF3a, ORF8 and N/ORF14 genes. We identified Senegal and Gambia, where the virus had been transferred from China and Europe in February-April as the sources of the Marseille-1 variant, which then most likely reached Marseille through Maghreb when French borders reopened. In France, this variant apparently remained almost limited to Marseille. In addition, it was significantly associated with a milder disease compared to clade 20A ancestor strains.CONCLUSIONOur results demonstrate that SARS-CoV-2 can genetically diversify rapidly, its variants can diffuse internationally and cause successive outbreaks.

VANIR—NextFlow Pipeline for Viral Variant Calling and de Novo Assembly of Nanopore and Illumina Reads for High-Quality dsDNA Viral Genomes

Human cytomegalovirus (HCMV), like other herpes and dsDNA viruses, possesses unique properties derived from their genome architecture. The HCMV genome is composed of two unique domains: long (L) and short (S). Each domain contains a central unique region (U; thus, UL and US, respectively) and two repeated regions (thus, TRL/IRL and TRS/IRS). Recombination between repetitive regions is possible, yielding four possible genomic isomers, found in equimolar proportion in any viral infective population. Frequent recombination and an altered selective landscape can give rise to the persistence, if not fixation, of diverse variants in culturized HCMV isolates. This phenomenon has already been discovered in AD169 and Towne strains, characterizing a 10 kbp deletion (ΔUL/b’) in commonly used viral strains. Other dsDNA viruses are known for their structural rearrangements and frequent recombination. VANIR (viral variant calling and de novo assembly using nanopore and illumina reads) is a novel analysis pipeline that benefits from both short-read (Illumina) and long-read sequencing technologies (Oxford Nanopore Technologies Ltd.) to assemble high-quality dsDNA viral genomes and detection of variants. Illumina and nanopore sequencing provide complementary information to the assembly and variant discovery. Assembly contiguity, structural variant, and repeat calling are greatly improved by nanopore read-length and base-calling and base confidence by Illumina reduced error rate and increased yield. This specialized bioinformatic analysis pipeline is encoded in the NextFlow pipeline manager and containerized in a Singularity image. This set-up allows for improved traceability, reproducibility, transportability, and speed. Through VANIR, novel point mutations and structural genome rearrangements are called from sequencing data, benefiting diversity research with attenuated lab-strains and wild-type viruses.