Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 17, 2023

Abstract Transmission bottlenecks limit the spread of novel mutations and reduce efficiency selection along a transmission chain. While increased force infection, receptor binding, or immune evasion may influence bottleneck size, relationship between transmissibility is unclear. Here we compare non-VOC SARS-CoV-2 lineages to those Alpha, Delta, Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0–1 single nucleotide variants (iSNV). From 64 pairs with detectable iSNV, identify per clade 1 (95% CI 1–1) for Omicron 2 2–2) non-VOC. These tight reflect low diversity at time transmission, which be more pronounced rapidly transmissible variants. Tight will development highly mutated VOC chains, adding evidence that over prolonged infections drive their evolution.

Language: Английский

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Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(8), P. 1484 - 1498

Published: March 11, 2024

Abstract Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 JN.1. Receptor binding immune evasion are recognized as two major drivers for evolution of receptor domain (RBD) spike (S) protein. However, underlying mechanism interplay between factors remains incompletely understood. Herein, we determined structures human ACE2 complexed with XBB RBDs. Based on ACE2/RBD these sub-variants a comparison known complex structures, found that R346T substitution in RBD enhanced upon an interaction residue R493, but not Q493, via involving long-range conformation changes. Furthermore, R493Q F486V exert balanced impact, through which capability was somewhat compromised to achieve optimal binding. We propose “two-steps-forward one-step-backward” model describe such compromise affinity during sub-variants.

Language: Английский

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Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 16, 2023

Abstract South Africa was among the first countries to detect SARS-CoV-2 Omicron variant. However, size of its BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, after BA.1/2 infer infection rates monitor changes in immune histories participants over time. found that infected more than half population, with reinfections vaccine breakthroughs accounting for > 60% all infections both rural urban sites. After wave, we few (< 6%) remained naïve population immunologic landscape is fragmented diverse infection/immunization histories. Prior ancestral strain, Beta, Delta variants provided 13%, 34%, 51% protection against infection, respectively. Hybrid immunity repeated prior reduced risks by 85% Our sheds light on rapidly shifting era provides context anticipating long-term circulation populations no longer virus.

Language: Английский

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The immune response to SARS-CoV-2 in people with HIV

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 184 - 196

Published: Oct. 11, 2023

Abstract This review examines the intersection of HIV and SARS-CoV-2 pandemics. People with (PWH) are a heterogeneous group that differ in their degree immune suppression, reconstitution, viral control. While COVID-19 those well-controlled infection poses no greater risk than for HIV-uninfected individuals, people advanced disease more vulnerable to poor outcomes. vaccines effective well tolerated majority PWH, though reduced vaccine efficacy, breakthrough infections faster waning effectiveness have been demonstrated PWH. is likely result suboptimal humoral cellular responses after vaccination. may also experience prolonged give rise new epidemiologically significant variants, but initiation or resumption antiretroviral therapy (ART) can effectively clear persistent infection. guidelines reflect these increased risks recommend prioritization vaccination additional booster doses PWH who moderately severely immunocompromised. We continued research monitoring infection, especially areas high burden.

Language: Английский

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Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease

JACS Au, Journal Year: 2023, Volume and Issue: 3(6), P. 1767 - 1774

Published: June 7, 2023

The SARS-CoV-2 main protease (M

Language: Английский

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Aryl hydrocarbon receptor is a proviral host factor and a candidate pan-SARS-CoV-2 therapeutic target

Science Advances, Journal Year: 2023, Volume and Issue: 9(22)

Published: May 31, 2023

The emergence of a series SARS-CoV-2 variants has necessitated the search for broad-spectrum antiviral targets. aryl hydrocarbon receptor (AhR) senses tryptophan metabolites and is an immune regulator. However, role AhR in infection whether can be used as target therapy against its are yet unclear. Here, we show that with activates signaling facilitates viral replication by interfering IFN-I-driven immunity up-regulating ACE2 expression. pharmacological blockade or knockout reduces variants' vitro. Drug targeting antagonists markedly reduced vivo ameliorated lung inflammation caused hamsters. Overall, was proviral host factor candidate host-directed variants, including Delta Omicron, potentially other future.

Language: Английский

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Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review

American Journal of Medicine Open, Journal Year: 2024, Volume and Issue: 11, P. 100068 - 100068

Published: Feb. 14, 2024

The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, the global economy. In order to save as many lives possible, precautions such social distancing, quarantine, testing policies were implemented, effective vaccines developed. A growing amount of data collected worldwide allowed characterization this new disease, which turned out be more complex than other common respiratory tract infections. An increasing number convalescents presented with a variety non-specific symptoms emerging after acute infection. This possible health problem was identified labelled long COVID. Since then, great effort been made by clinicians scientific community understand underlying mechanisms develop preventive measures treatment. role autoimmunity induced infection development COVID is discussed review. We aim deliver description several conditions an autoimmune background observed COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome related thrombosis, Kawasaki disease highlighting relationship between autoimmunity. However, further studies are required determine its true clinical significance.

Language: Английский

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Using big sequencing data to identify chronic SARS-Coronavirus-2 infections

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 20, 2024

Language: Английский

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Next-generation treatments: Immunotherapy and advanced therapies for COVID-19

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e26423 - e26423

Published: Feb. 19, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS recent decades, underscoring their high potential infectivity humans. Insights from previous have played a significant role developing effective strategies to mitigate the global impact SARS-CoV-2. As January 7, 2024, there been 774,075,242 confirmed cases worldwide. To date, 13.59 billion vaccine doses administered, 7,012,986 documented fatalities (https://www.who.int/)Despite progress addressing rapid evolution SARS-CoV-2 challenges human defenses, presenting ongoing challenges. emergence new lineages, shaped mutation recombination processes, has led successive waves infections. This scenario reveals need for next-generation vaccines as crucial requirement ensuring protection against demand calls formulations that trigger robust adaptive immune response without leading inflammation linked with infection.Key mutations detected Spike protein, critical target neutralizing antibodies design —specifically within Receptor Binding Domain region Omicron variant lineages (B.1.1.529), currently dominant worldwide, intensified concerns due association immunity evasion vaccinations infections.As world deals this evolving threat, narrative extends realm emerging variants, each displaying implications remain largely misunderstood. Notably, JN.1 lineage is gaining prevalence, early findings suggest it stands among immune-evading characteristic attributed its L455S. Moreover, detrimental consequences novel bear particularly on immunocompromised individuals older adults. Immunocompromised face such suboptimal responses vaccines, rendering them more susceptible disease. Similarly, adults an increased risk disease presence comorbid conditions, find themselves at heightened vulnerability develop Thus, recognizing these intricate factors effectively tailoring public health protect vulnerable populations. In context, review aims describe, analyze, discuss current treatments encompassing immunotherapeutic approaches advanced therapies complements will offer solutions counter disadvantages existing options. Preliminary outcomes show virus address immunomodulatory associated COVID-19. Furthermore, capacity promote tissue repair demonstrated, which can be noteworthy who stand actors landscape possess broader potential, offering wide range variants enhancing ability constant virus. are projected treatment alternatives managing Chronic Post-COVID-19 syndromeand long-term complications.

Language: Английский

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Predicting Antiviral Resistance Mutations in SARS-CoV-2 Main Protease with Computational and Experimental Screening

Biochemistry, Journal Year: 2022, Volume and Issue: 61(22), P. 2495 - 2505

Published: Nov. 3, 2022

The main protease (Mpro) of SARS-CoV-2 is essential for viral replication and has been the focus many drug discovery efforts since start COVID-19 pandemic. Nirmatrelvir (NTV) an inhibitor Mpro that used in combination Paxlovid treatment mild to moderate COVID-19. However, with increased use NTV across globe, there a possibility future lineages will evolve resistance NTV. Early prediction monitoring mutations could allow measures slow spread development new compounds activity against resistant strains. In this work, we have silico mutational scanning docking identify potential mutations. Subsequent vitro experiments revealed five (N142L, E166M, Q189E, Q189I, Q192T) reduce potency previously identified non-covalent cyclic peptide Mpro. E166M mutation reduced half-maximal inhibitory concentration (IC50) 24-fold 118-fold inhibitor. Our findings inform ongoing genomic surveillance emerging lineages.

Language: Английский

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