Biology subjects

Graichen, L.

Publications and source records attributed to Graichen, L..

9 recordsLinked to original sources

bioRxiv2026

Epidemiology and virological characteristics of the emerging SARS-CoV-2 variant PJ.2.1

SARS-CoV-2 continues to circulate globally at high levels and to evolve into new variants. Recently, a new saltation variant harbouring a highly mutated spike protein, PJ.2.1, emerged in North America. Here, we provide a brief epidemiological and virological characterization of PJ.2.1 and cocirculating variants. We report that PJ.2.1 is spreading in the USA, Canada, and Spain and mainly infects individuals aged 60 years and older, as do most other variants, with the exception of BA.3.2, which preferentially infects individuals aged 0-9 years. PJ.2.1 was less susceptible to inhibition by an antibody against ACE2 than were the other variants, indicating increased ACE2 binding. In contrast, PJ.2.1 did not show augmented evasion of antibodies from vaccinees who had received the LP.8.1-adapted vaccine compared with most other variants analysed. These results suggest that augmented ACE2 affinity rather than increased antibody evasion might drive the current, rapid spread of PJ.2.1.

microbiology↗

bioRxiv2024

ACE2-independent sarbecovirus cell entry is supported by TMPRSS2-related enzymes and reduces sensitivity to antibody-mediated neutralization

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract. In contrast, two bat sarbecovirus S proteins drove cell entry in an ACE2-independent, trypsin-dependent fashion and several ACE2-dependent S proteins could switch to the ACE2-independent entry pathway when exposed to trypsin. Several TMPRSS2-related cellular proteases but not the insertion of a multibasic cleavage site into the S protein allowed for ACE2-independent entry in the absence of trypsin and may support viral spread in the respiratory tract. Finally, the pan-sarbecovirus antibody S2H97 enhanced cell entry driven by two S proteins and this effect was reversed by trypsin. Similarly, plasma from quadruple vaccinated individuals neutralized entry driven by all S proteins studied, and use of the ACE2-independent, trypsin-dependent pathway reduced neutralization sensitivity. In sum, our study reports a pathway for entry into human cells that is ACE2-independent, supported by TMPRSS2-related proteases and associated with antibody evasion.

molecular biology↗

bioRxiv2024

Virological traits of the SARS-CoV-2 BA.2.87.1 lineage

The highly mutated SARS-CoV-2 BA.2.87.1 lineage was recently detected in South Africa, but its transmissibility is unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for high transmissibility.

molecular biology↗

bioRxiv2022

Entorhinal grid-like codes and time-locked network dynamics track others navigating through space

Navigating through crowded, dynamically changing social environments requires the ability to keep track of other individuals. Grid cells in the entorhinal cortex are a central component of self-related navigation but whether they also track others movement is unclear. Here, we propose that entorhinal grid-like codes make an essential contribution to socio-spatial navigation. Sixty human participants underwent functional magnetic resonance imaging (fMRI) while observing and re-tracing different paths of a demonstrator that navigated a virtual reality environment. Results revealed that grid-like codes in the entorhinal cortex tracked the other individual navigating through space. Further, the activity of grid-like codes was time-locked to increases in co-activation and entorhinal-cortical connectivity that included the striatum, the hippocampus, parahippocampal and right posterior parietal cortices, altogether modulated by accuracy when subsequently re-tracing the paths. This suggests that network dynamics time-locked to entorhinal grid-cell-related activity might serve to distribute information about the socio-spatial map throughout the brain.

neuroscience↗

bioRxiv2021

The Omicron variant is highly resistant against antibody-mediated neutralization - implications for control of the COVID-19 pandemic

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

microbiology↗

bioRxiv2021

Increased lung cell entry of B.1.617.2 and evasion of antibodies induced by infection and BNT162b2 vaccination

The delta variant of SARS-CoV-2, B.1.617.2, emerged in India and has subsequently spread to over 80 countries. B.1.617.2 rapidly replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for COVID-19 therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although with lower efficiency as compared to B.1.351. Further, we found that B.1.617.2 is resistant against Bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3-lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.1.617.2 as an immune evasion variant with increased capacity to enter and fuse lung cells.

molecular biology↗

bioRxiv2021

SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

molecular biology↗

bioRxiv2021

SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization

Transmission of SARS-CoV-2 from humans to farmed mink was observed in Europe and the US. In the infected animals viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health and resulted in mass culling of mink. Here, we report that mutations frequently found in the S proteins of SARS-CoV-2 from mink were mostly compatible with efficient entry into human cells and its inhibition by soluble ACE2. In contrast, mutation Y453F reduced neutralization by an antibody with emergency use authorization for COVID-19 therapy and by sera/plasma from COVID-19 patients. These results suggest that antibody responses induced upon infection or certain antibodies used for treatment might offer insufficient protection against SARS-CoV-2 variants from mink.

molecular biology↗

bioRxiv2021

SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination

The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic.

molecular biology↗