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description Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37964065&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37964065&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37726446&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37726446&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2023 United StatesPublisher:Springer Science and Business Media LLC Funded by:NIH | A Data Resource for Analy..., NIH | MHC Variation in Host Res..., NIH | Defining Variation in the...NIH| A Data Resource for Analyzing Blood and Marrow Transplants ,NIH| MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes ,NIH| Defining Variation in the Natural Killer Cell Receptome in Human PopulationsAuthors: Danillo G. Augusto; Lawton D. Murdolo; Demetra S. M. Chatzileontiadou; Joseph J. Sabatino; +35 AuthorsDanillo G. Augusto; Lawton D. Murdolo; Demetra S. M. Chatzileontiadou; Joseph J. Sabatino; Tasneem Yusufali; Noah D. Peyser; Xochitl Butcher; Kerry Kizer; Karoline Guthrie; Victoria W. Murray; Vivian Pae; Sannidhi Sarvadhavabhatla; Fiona Beltran; Gurjot S. Gill; Kara L. Lynch; Cassandra Yun; Colin T. Maguire; Michael J. Peluso; Rebecca Hoh; Timothy J. Henrich; Steven G. Deeks; Michelle Davidson; Scott Lu; Sarah A. Goldberg; J. Daniel Kelly; Jeffrey N. Martin; Cynthia A. Vierra-Green; Stephen R. Spellman; David J. Langton; Michael J. Dewar-Oldis; Corey Smith; Peter J. Barnard; Sulggi Lee; Gregory M. Marcus; Jeffrey E. Olgin; Mark J. Pletcher; Martin Maiers; Stephanie Gras; Jill A. Hollenbach;AbstractStudies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1–4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.
eScholarship - Unive... arrow_drop_down eScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06331-x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu44 citations 44 popularity Top 1% influence Top 10% impulse Top 1% Powered by BIP!more_vert eScholarship - Unive... arrow_drop_down eScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06331-x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Research , Preprint , Other literature type 2023Publisher:Center for Open Science Authors: Philipp Sprengholz; Luca Henkel; Robert Böhm; Cornelia Betsch;Philipp Sprengholz; Luca Henkel; Robert Böhm; Cornelia Betsch;handle: 10419/278679
pmid: 37914928
How people recall the SARS-CoV2 pandemic is likely to prove crucial in future societal debates on pandemic preparedness and appropriate political action. Beyond simple forgetting, previous research suggests that recall may be distorted by strong motivations and anchoring perceptions on the current situation. Here, based on four studies across 11 countries (total N = 10,776), we show that recall of perceived risk, trust in institutions and protective behaviours depended strongly on current evaluations. While both vaccinated and unvaccinated individuals were affected by this bias, people who identified strongly with their vaccination status—whether vaccinated or unvaccinated—tended to exhibit greater and, importantly, opposite distortions of recall. Biased recall was not reduced by providing information about common recall errors or small monetary incentives for accurate recall, but partially by high incentives. Thus, it seems that motivation and identity influence the direction in which the recall of the past is distorted. Biased recall was further related to the evaluation of past political action and future behavioural intent, including adhering to regulations during a future pandemic or punishing politicians and scientists. Taken together, the findings indicate that historical narratives about the COVID-19 pandemic are motivationally biased, sustain societal polarization and affect preparation for future pandemics. Consequently, future measures must look beyond immediate public health implications to the longer-term consequences for societal cohesion and trust.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.31234/osf.io/r84dc&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.31234/osf.io/r84dc&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint , Article 2023Publisher:Cold Spring Harbor Laboratory Ayijiang Yisimayi; Weiliang Song; Jing Wang; Fanchong Jian; Yuanling Yu; Xiaosu Chen; Yanli Xu; Sijie Yang; Xiao Niu; Tianhe Xiao; Jing Wang; Lijuan Zhao; Haiyan Sun; Ran An; Na Zhang; Yao Wang; Peng Wang; Lingling Yu; Zhe Lv; Qingqing Gu; Fei Shao; Ronghua Jin; Zhongyang Shen; Xiaoliang Sunney Xie; Youchun Wang; Yunlong Cao;pmid: 37993710
AbstractThe continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.51,2and XBB.1.163,4, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters5-9. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.05.01.538516&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 29 citations 29 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.05.01.538516&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023Publisher:Springer Science and Business Media LLC Funded by:NIH | Supporting RNAstructure: ...NIH| Supporting RNAstructure: Software for RNA AnalysisHe Zhang; Liang Zhang; Ang Lin; Congcong Xu; Ziyu Li; Kaibo Liu; Boxiang Liu; Xiaopin Ma; Fanfan Zhao; Huiling Jiang; Chunxiu Chen; Haifa Shen; Hangwen Li; David H. Mathews; Yujian Zhang; Liang Huang;Messenger RNA (mRNA) vaccines are being used for COVID-19, but still suffer from the critical issue of mRNA instability and degradation, which is a major obstacle in the storage, distribution, and efficacy of the vaccine. Previous work showed that optimizing secondary structure stability lengthens mRNA half-life, which, together with optimal codons, increases protein expression. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage to improve mRNA efficiency. However, due to synonymous codons, the mRNA design space is prohibitively large, e.g., there are $\sim\!10^{632}$ mRNAs for the SARS-CoV-2 Spike protein, which poses insurmountable challenges to previous methods. Here we provide a surprisingly simple solution to this hard problem by reducing it to a classical problem in computational linguistics, where finding the optimal mRNA is akin to finding the most likely sentence among similar sounding alternatives. Our algorithm, named LinearDesign, takes only 11 minutes for the Spike protein, and can jointly optimize stability and codon usage. Experimentally, without chemical modification, our designs substantially improve mRNA half-life and protein expression in vitro, and dramatically increase antibody response by up to 23$\times$ in vivo, compared to the codon-optimized benchmark. Our work enables the exploration of highly stable and efficient designs that are previously unreachable and is a timely tool not only for vaccines but also for mRNA medicine encoding all therapeutic proteins (e.g., monoclonal antibodies and anti-cancer drugs). Comment: 17 pages for main text; 24 pages of supporting information; 4+11=15 figures; 2 tables (both in supporting information)
Nature arrow_drop_down arXiv.org e-Print ArchiveOther literature type . Preprint . 2020Data sources: arXiv.org e-Print Archivehttps://doi.org/10.48550/arxiv...Article . 2020License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06127-z&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 42 citations 42 popularity Top 10% influence Average impulse Top 1% Powered by BIP!more_vert Nature arrow_drop_down arXiv.org e-Print ArchiveOther literature type . Preprint . 2020Data sources: arXiv.org e-Print Archivehttps://doi.org/10.48550/arxiv...Article . 2020License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06127-z&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Preprint 2023 NetherlandsPublisher:Cold Spring Harbor Laboratory Funded by:EC | SWEETPROMISE, NWO | The Institute for Chemica...EC| SWEETPROMISE ,NWO| The Institute for Chemical Immunology ICIMatti F. Pronker; Robert Creutznacher; Ieva Drulyte; Ruben J.G. Hulswit; Zeshi Li; Frank J.M. van Kuppeveld; Joost Snijder; Yifei Lang; Berend-Jan Bosch; Geert-Jan Boons; Martin Frank; Raoul J. de Groot; Daniel L. Hurdiss;AbstractCoronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1–5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.04.20.536837&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 8 citations 8 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.04.20.536837&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37020009&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37020009&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=36750677&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=36750677&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type , Article , Preprint 2023 United KingdomPublisher:Cold Spring Harbor Laboratory Theo Sanderson; Ryan Hisner; I’ah Donovan-Banfield; Hassan Hartman; Alessandra Løchen; Thomas P. Peacock; Christopher Ruis;AbstractMolnupiravir, an antiviral medication widely used against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus and many will be lethal; thus, molnupiravir-induced elevated mutation rates reduce viral load1,2. However, if some patients treated with molnupiravir do not fully clear the SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, are found almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age groups with widespread use of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onward transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm a direct association between these high G-to-A branches and the use of molnupiravir.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.26.23284998&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 32 citations 32 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.26.23284998&type=result"></script>'); --> </script>
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description Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37964065&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37964065&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37726446&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37726446&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2023 United StatesPublisher:Springer Science and Business Media LLC Funded by:NIH | A Data Resource for Analy..., NIH | MHC Variation in Host Res..., NIH | Defining Variation in the...NIH| A Data Resource for Analyzing Blood and Marrow Transplants ,NIH| MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes ,NIH| Defining Variation in the Natural Killer Cell Receptome in Human PopulationsAuthors: Danillo G. Augusto; Lawton D. Murdolo; Demetra S. M. Chatzileontiadou; Joseph J. Sabatino; +35 AuthorsDanillo G. Augusto; Lawton D. Murdolo; Demetra S. M. Chatzileontiadou; Joseph J. Sabatino; Tasneem Yusufali; Noah D. Peyser; Xochitl Butcher; Kerry Kizer; Karoline Guthrie; Victoria W. Murray; Vivian Pae; Sannidhi Sarvadhavabhatla; Fiona Beltran; Gurjot S. Gill; Kara L. Lynch; Cassandra Yun; Colin T. Maguire; Michael J. Peluso; Rebecca Hoh; Timothy J. Henrich; Steven G. Deeks; Michelle Davidson; Scott Lu; Sarah A. Goldberg; J. Daniel Kelly; Jeffrey N. Martin; Cynthia A. Vierra-Green; Stephen R. Spellman; David J. Langton; Michael J. Dewar-Oldis; Corey Smith; Peter J. Barnard; Sulggi Lee; Gregory M. Marcus; Jeffrey E. Olgin; Mark J. Pletcher; Martin Maiers; Stephanie Gras; Jill A. Hollenbach;AbstractStudies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1–4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.
eScholarship - Unive... arrow_drop_down eScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06331-x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu44 citations 44 popularity Top 1% influence Top 10% impulse Top 1% Powered by BIP!more_vert eScholarship - Unive... arrow_drop_down eScholarship - University of CaliforniaArticle . 2023Data sources: eScholarship - University of Californiaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06331-x&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Research , Preprint , Other literature type 2023Publisher:Center for Open Science Authors: Philipp Sprengholz; Luca Henkel; Robert Böhm; Cornelia Betsch;Philipp Sprengholz; Luca Henkel; Robert Böhm; Cornelia Betsch;handle: 10419/278679
pmid: 37914928
How people recall the SARS-CoV2 pandemic is likely to prove crucial in future societal debates on pandemic preparedness and appropriate political action. Beyond simple forgetting, previous research suggests that recall may be distorted by strong motivations and anchoring perceptions on the current situation. Here, based on four studies across 11 countries (total N = 10,776), we show that recall of perceived risk, trust in institutions and protective behaviours depended strongly on current evaluations. While both vaccinated and unvaccinated individuals were affected by this bias, people who identified strongly with their vaccination status—whether vaccinated or unvaccinated—tended to exhibit greater and, importantly, opposite distortions of recall. Biased recall was not reduced by providing information about common recall errors or small monetary incentives for accurate recall, but partially by high incentives. Thus, it seems that motivation and identity influence the direction in which the recall of the past is distorted. Biased recall was further related to the evaluation of past political action and future behavioural intent, including adhering to regulations during a future pandemic or punishing politicians and scientists. Taken together, the findings indicate that historical narratives about the COVID-19 pandemic are motivationally biased, sustain societal polarization and affect preparation for future pandemics. Consequently, future measures must look beyond immediate public health implications to the longer-term consequences for societal cohesion and trust.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.31234/osf.io/r84dc&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 3 citations 3 popularity Top 10% influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.31234/osf.io/r84dc&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint , Article 2023Publisher:Cold Spring Harbor Laboratory Ayijiang Yisimayi; Weiliang Song; Jing Wang; Fanchong Jian; Yuanling Yu; Xiaosu Chen; Yanli Xu; Sijie Yang; Xiao Niu; Tianhe Xiao; Jing Wang; Lijuan Zhao; Haiyan Sun; Ran An; Na Zhang; Yao Wang; Peng Wang; Lingling Yu; Zhe Lv; Qingqing Gu; Fei Shao; Ronghua Jin; Zhongyang Shen; Xiaoliang Sunney Xie; Youchun Wang; Yunlong Cao;pmid: 37993710
AbstractThe continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.51,2and XBB.1.163,4, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters5-9. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.05.01.538516&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 29 citations 29 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.05.01.538516&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2023Publisher:Springer Science and Business Media LLC Funded by:NIH | Supporting RNAstructure: ...NIH| Supporting RNAstructure: Software for RNA AnalysisHe Zhang; Liang Zhang; Ang Lin; Congcong Xu; Ziyu Li; Kaibo Liu; Boxiang Liu; Xiaopin Ma; Fanfan Zhao; Huiling Jiang; Chunxiu Chen; Haifa Shen; Hangwen Li; David H. Mathews; Yujian Zhang; Liang Huang;Messenger RNA (mRNA) vaccines are being used for COVID-19, but still suffer from the critical issue of mRNA instability and degradation, which is a major obstacle in the storage, distribution, and efficacy of the vaccine. Previous work showed that optimizing secondary structure stability lengthens mRNA half-life, which, together with optimal codons, increases protein expression. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage to improve mRNA efficiency. However, due to synonymous codons, the mRNA design space is prohibitively large, e.g., there are $\sim\!10^{632}$ mRNAs for the SARS-CoV-2 Spike protein, which poses insurmountable challenges to previous methods. Here we provide a surprisingly simple solution to this hard problem by reducing it to a classical problem in computational linguistics, where finding the optimal mRNA is akin to finding the most likely sentence among similar sounding alternatives. Our algorithm, named LinearDesign, takes only 11 minutes for the Spike protein, and can jointly optimize stability and codon usage. Experimentally, without chemical modification, our designs substantially improve mRNA half-life and protein expression in vitro, and dramatically increase antibody response by up to 23$\times$ in vivo, compared to the codon-optimized benchmark. Our work enables the exploration of highly stable and efficient designs that are previously unreachable and is a timely tool not only for vaccines but also for mRNA medicine encoding all therapeutic proteins (e.g., monoclonal antibodies and anti-cancer drugs). Comment: 17 pages for main text; 24 pages of supporting information; 4+11=15 figures; 2 tables (both in supporting information)
Nature arrow_drop_down arXiv.org e-Print ArchiveOther literature type . Preprint . 2020Data sources: arXiv.org e-Print Archivehttps://doi.org/10.48550/arxiv...Article . 2020License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06127-z&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 42 citations 42 popularity Top 10% influence Average impulse Top 1% Powered by BIP!more_vert Nature arrow_drop_down arXiv.org e-Print ArchiveOther literature type . Preprint . 2020Data sources: arXiv.org e-Print Archivehttps://doi.org/10.48550/arxiv...Article . 2020License: arXiv Non-Exclusive DistributionData sources: Dataciteadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41586-023-06127-z&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Preprint 2023 NetherlandsPublisher:Cold Spring Harbor Laboratory Funded by:EC | SWEETPROMISE, NWO | The Institute for Chemica...EC| SWEETPROMISE ,NWO| The Institute for Chemical Immunology ICIMatti F. Pronker; Robert Creutznacher; Ieva Drulyte; Ruben J.G. Hulswit; Zeshi Li; Frank J.M. van Kuppeveld; Joost Snijder; Yifei Lang; Berend-Jan Bosch; Geert-Jan Boons; Martin Frank; Raoul J. de Groot; Daniel L. Hurdiss;AbstractCoronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1–5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.04.20.536837&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 8 citations 8 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.04.20.536837&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37020009&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=37020009&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type 2023add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=36750677&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routesbronze 0 citations 0 popularity Average influence Average impulse Average Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=36750677&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type , Article , Preprint 2023 United KingdomPublisher:Cold Spring Harbor Laboratory Theo Sanderson; Ryan Hisner; I’ah Donovan-Banfield; Hassan Hartman; Alessandra Løchen; Thomas P. Peacock; Christopher Ruis;AbstractMolnupiravir, an antiviral medication widely used against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus and many will be lethal; thus, molnupiravir-induced elevated mutation rates reduce viral load1,2. However, if some patients treated with molnupiravir do not fully clear the SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, are found almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age groups with widespread use of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onward transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm a direct association between these high G-to-A branches and the use of molnupiravir.
add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.26.23284998&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 32 citations 32 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2023.01.26.23284998&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu