The evolution of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(6), P. 361 - 379

Published: April 5, 2023

Language: Английский

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Efficient evolution of human antibodies from general protein language models

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(2), P. 275 - 283

Published: April 24, 2023

Abstract Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report general protein language models can efficiently evolve human antibodies by mutations are evolutionarily plausible, despite providing the model with no information about target antigen, binding specificity or structure. We performed language-model-guided affinity maturation seven antibodies, screening 20 fewer variants each antibody across only two rounds laboratory evolution, and improved affinities four clinically relevant, highly mature up to sevenfold three unmatured 160-fold, many designs also demonstrating favorable thermostability viral neutralization activity against Ebola severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same improve efficient diverse families selection pressures, including antibiotic resistance enzyme activity, these results generalize settings.

Language: Английский

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CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 29, 2023

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is latest variant concern, and BA.5 replacing BA.2 become main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed gene sequencing, making time-consuming processes expensive instrumentation indispensable. In this study, we developed rapid ultrasensitive electrochemical biosensor achieve goals high sensitivity, ability distinguishing variants, direct detection RNAs from viruses simultaneously. We used electrodes made MXene-AuNP (gold nanoparticle) composites improved sensitivity CRISPR/Cas13a system specificity in detecting single-base mutation clinical samples. Our will be excellent supplement RT-qPCR method enabling early diagnosis quick distinguishment Omicron more potential that might arise future.

Language: Английский

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Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

Science Advances, Journal Year: 2023, Volume and Issue: 9(13)

Published: March 31, 2023

Vaccines and drugs have helped reduce disease severity blunt the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ongoing virus transmission, continuous evolution, increasing selective pressures potential to yield viral variants capable resisting these interventions. Here, we investigate susceptibility natural main protease [Mpro; 3C-like (3CLpro)] SARS-CoV-2 inhibitors. Multiple single amino acid changes in Mpro confer resistance nirmatrelvir (the active component Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different mutation profile. Importantly, phylogenetic analyses indicate that several resistant pre-existed introduction into human population are spreading. These results encourage monitoring development inhibitors other antiviral with mechanisms action profiles for combinatorial therapy.

Language: Английский

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A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes

Nature, Journal Year: 2023, Volume and Issue: 623(7987), P. 594 - 600

Published: Sept. 25, 2023

Molnupiravir, 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 are likely to be deleterious and many will lethal; thus, molnupiravir-induced elevated mutation rates reduce viral load1,2. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could potential for onward transmission of molnupiravir-mutated viruses. Here we show that sequencing databases contain extensive evidence mutagenesis. Using a systematic approach, find specific class long phylogenetic branches, distinguished high proportion G-to-A C-to-T mutations, found almost exclusively sequences from 2022, after introduction treatment, countries age groups widespread use drug. We identify mutational spectrum, preferred nucleotide contexts, viruses known have been its signature matches seen these cases molnupiravir-derived lineages. Finally, analyse treatment records confirm direct association between branches molnupiravir.

Language: Английский

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SARS-CoV-2 biology and host interactions

Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(4), P. 206 - 225

Published: Jan. 15, 2024

Language: Английский

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Insights for COVID-19 in 2023

Revista Española de Quimioterapia, Journal Year: 2022, Volume and Issue: 36(2), P. 114 - 124

Published: Dec. 12, 2022

Predictions for a near end of the pandemic by World Health Organization should be interpreted with caution. Current evidence indicates that efficacy fourth dose classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection its predominant variant (Omicron). However, high against severe symptomatic infection, hospitalization death. The new being introduced are bivalent active Omicron variants. Potential to coming year include vaccine based on recombinant protein emulates receptor binding domain Spike under development Spanish company Hipra, as well nasal oral administration. Available information suggests COVID-19 can administered association influenza vaccination without particular complications. New drugs COVID-19, both antiviral anti-inflammatory, investigation, but this does not seem case monoclonal antibodies. indication use masks some circumstances will maintained next view accumulation scientific data their efficacy. Finally, long COVID Post-COVID syndrome may continue affect very proportion patients who have had disease, requiring combined diagnostic therapeutic resources.

Language: Английский

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Immune evasion and ACE2 binding affinity contribute to SARS-CoV-2 evolution

Nature Ecology & Evolution, Journal Year: 2023, Volume and Issue: 7(9), P. 1457 - 1466

Published: July 13, 2023

Language: Английский

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SARS-CoV-2 and innate immunity: the good, the bad, and the “goldilocks”

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 171 - 183

Published: Nov. 20, 2023

Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.

Language: Английский

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Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the USA

Infectious Diseases and Therapy, Journal Year: 2023, Volume and Issue: 12(2), P. 607 - 621

Published: Jan. 11, 2023

Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness sotrovimab in reducing risk 30-day all-cause hospitalization and/or mortality was evaluated period when prevalence circulating SARS-CoV-2 variants changed between Delta Omicron USA.A retrospective analysis conducted de-identified patients diagnosed COVID-19 1 September 30 2022 FAIR Health National Private Insurance Claims database. Patients meeting criteria were divided into two cohorts: not treated mAb ("no mAb"). All-cause hospitalizations facility-reported ≤ days diagnosis ("30-day or mortality") identified. Multivariable propensity score-matched Poisson logistic regressions estimate adjusted relative (RR) odds each cohort.Compared no cohort (n = 1,514,868), 15,633) older higher proportion conditions. In cohort, 84,307 (5.57%) hospitalized 8167 (0.54%) deaths identified, while 418 (2.67%) 13 (0.08%) After adjusting potential confounders, 55% lower (RR 0.45, 95% CI 0.41-0.49) an 85% 0.15, 0.08-0.29). Monthly, 2022, RR reduction maintained, ranging 46% 71% compared cohort; uncertain, wide confidence intervals due small sample size.Sotrovimab associated reduced versus treatment. Clinical persisted during early variant waves among all subgroups assessed.

Language: Английский

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