SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(2), P. 112 - 124

Published: Oct. 28, 2022

Language: Английский

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Structural biology of SARS-CoV-2: open the door for novel therapies

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Jan. 27, 2022

Abstract Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of pandemic disease COVID-19, which so far without efficacious treatment. The discovery therapy reagents for treating COVID-19 are urgently needed, and structures potential drug-target proteins in viral life cycle particularly important. SARS-CoV-2, a member Orthocoronavirinae subfamily containing largest RNA genome, encodes 29 including nonstructural, structural accessory involved adsorption, entry uncoating, nucleic acid replication transcription, assembly release, etc. These individually act as partner machinery or forming complexes with host cellular factors to participate essential physiological activities. This review summarizes representative typically agents that target SARS-CoV-2 some critical pathogenesis, providing insights into mechanisms underlying infection, prevention Indeed, these studies open door COVID therapies, leading ways prevent treat especially, treatment caused by variants imperative.

Language: Английский

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A Global Map of COVID-19 Vaccine Acceptance Rates per Country: An Updated Concise Narrative Review

Journal of Multidisciplinary Healthcare, Journal Year: 2022, Volume and Issue: Volume 15, P. 21 - 45

Published: Jan. 1, 2022

Abstract: The delay or refusal of vaccination, which defines vaccine hesitancy, is a major challenge to successful control COVID-19 epidemic. huge number publications addressing hesitancy necessitates periodic review provide concise summary acceptance rates worldwide. In the current narrative review, data on were retrieved from surveys in 114 countries/territories. East and Southern Africa (n = 9), highest rate was reported Ethiopia (92%), while lowest Zimbabwe (50%). West/Central 13), Niger (93%), Cameroon (15%). Asia Pacific 16), Nepal Vietnam (97%), Hong Kong (42%). Eastern Europe/Central 7), Montenegro (69%) Kazakhstan (64%), Russia (30%). Latin America Caribbean 20), Mexico (88%), Haiti (43%). Middle East/North (MENA, n 22), Tunisia Iraq (13%). Western/Central Europe North 27), Canada (91%) Norway (89%), Cyprus Portugal (35%). ≥ 60% seen 72/114 countries/territories, compared 42 countries/territories with between 13% 59%. phenomenon appeared more pronounced MENA, Central Asia, Africa. More studies are recommended Africa, address intentions general public get vaccination. Keywords: SARS-CoV-2, hesitance, resistance, rejection, willingness vaccinate, intention vaccinate

Language: Английский

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Infection With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant Is Associated With Higher Recovery of Infectious Virus Compared to the Alpha Variant in Both Unvaccinated and Vaccinated Individuals

Clinical Infectious Diseases, Journal Year: 2021, Volume and Issue: 75(1), P. e715 - e725

Published: Dec. 14, 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.617.2 (Delta) displaced B.1.1.7 (Alpha) and is associated with increases in disease 2019 (COVID-19) cases, greater transmissibility, higher viral RNA loads, but data are lacking regarding the infectious virus load antiviral antibody levels nasal tract.Whole genome sequencing, cycle threshold (Ct) values, virus, anti-SARS-CoV-2 immunoglobulin G (IgG) levels, clinical chart reviews were combined to characterize SARS-CoV-2 lineages circulating National Capital Region between January September 2021 differentiate infections vaccinated unvaccinated individuals by Delta, Alpha, B.1.2 (the predominant lineage prior Alpha) variants.The Delta Alpha constitute 99% August 2021. In infections, 28.5% breakthrough cases fully compared 4% infected cohort. Breakthrough both cohorts comorbidities, only a significant increase median days after vaccination. More than 74% samples had <30% from recovery variants was low local IgG.Infection more frequent not an severity individuals. Infectious correlated presence amounts IgG specimens.

Language: Английский

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Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Aug. 20, 2021

Abstract Background The emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. Delta has been greater transmissibility higher viral RNA loads both unvaccinated fully vaccinated individuals. Data lacking regarding infectious virus load infected individuals how that compares to other lineages. Methods Whole genome sequencing 2,785 clinical isolates was used characterize prevalence lineages circulating National Capital Region between January July 2021. Clinical chart reviews were performed for Delta, Alpha, B.1.2 (a control predominant lineage prior VOCs) variants evaluate disease severity outcome Cycle threshold values (Cts) compared. presence determined using Vero-TMPRSS2 cells anti-SARS-CoV-2 IgG levels from upper respiratory specimen. An analysis infection populations performed. Results Alpha constitute 88.2% by July, increased breakthrough infections mostly symptomatic when compared infections, though it important note there a significantly longer period time vaccination infections. recovery on cell culture groups. impact reducing samples only observed but strongly low localized variants. A comparison Ct showed significant decrease no differences Conclusions Our data indicate decreased antiviral levels. Measures reduce transmission addition increasing vaccinations rates have be implemented spread. Funding NIH/NIAID Center Excellence Influenza Research Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department health, Centers Disease Control Prevention 75D30121C11061.

Language: Английский

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The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines

The Brazilian Journal of Infectious Diseases, Journal Year: 2021, Volume and Issue: 25(4), P. 101606 - 101606

Published: July 1, 2021

Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use humans. Subunit one or more antigens suitable eliciting a robust immune response. However, major concern is efficacy and elicited antibodies to neutralize variants like B.1.1.7 (Alpha), B.1.351 (Beta) P1 (Gamma), B.1.617 (Delta) C.37 (Lambda). The Spike (S) potential fragment as an antigen vaccine development. This plays crucial role step process, it binds Angiotensin-Converting Enzyme 2 (ACE2) receptor enters host cell after binding. Immunization-induced specific against binding domain (RBD) may block effectively prevent virus invasion. focus this review impact spike mutated SARS-CoV2 (Alpha, Beta, Gamma, Delta, Lambda) on recombinant vaccines. To date, low no significant Alpha Delta has reported. Such Lambda be even greater compared variant. Nonetheless, comprehensive analyses are needed assess real brought about by variants.

Language: Английский

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Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity

Seminars in Immunology, Journal Year: 2021, Volume and Issue: 55, P. 101533 - 101533

Published: June 1, 2021

Responsible for more than 4.9 million deaths so far, COVID-19, caused by SARS-CoV-2, is instigating devastating effects on the global health care system whose impacts could be longer years to come. Acquiring a comprehensive knowledge of host-virus interaction critical designing effective vaccines and/or drugs. Understanding evolution virus and impact genetic variability host immune evasion vaccine efficacy helpful design novel strategies minimize emerging variants concern (VOC). Most under development in current use target spike protein owning its unique function receptor binding, relatively conserved nature, potent immunogenicity inducing neutralizing antibodies, being good T cell responses. However, SARS-CoV-2 strains are exhibiting which affect antibody-based therapies addition enhancing viral mechanisms. Currently, degree mutations immunity vaccination, ability confer protection against attracts much attention. This review discusses implications vaccine-induced forward directions contribute future studies focusing immunotherapies consider evolution. Combining derived from different regions that boost both humoral cellular wings adaptive best options cope with VOC.

Language: Английский

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Roles and functions of SARS-CoV-2 proteins in host immune evasion

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 8, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory that play indispensable roles to suppress production signaling type I III interferons (IFNs). In this review, we discussed functions underlying mechanisms different evade by suppressing IFN-β TANK-binding kinase 1 (TBK1)/interferon factor 3 (IRF3)/signal transducer activator transcription (STAT)1 STAT2 phosphorylation. We also described viral inhibiting nuclear translocation IRF3, factor-κB (NF-κB), STATs. To date, following including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, Membrane (M) protein have been well studied. However, detailed evasion NSP5, ORF3b, ORF9c, Nucleocapsid (N) are not elucidated. Additionally, elaborated perspectives proteins.

Language: Английский

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SARS-CoV-2: Evolution and Emergence of New Viral Variants

Viruses, Journal Year: 2022, Volume and Issue: 14(4), P. 653 - 653

Published: March 22, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for disease 2019 (COVID-19). high rate of mutation this virus associated with a quick emergence new viral variants that have been rapidly spreading worldwide. Several mutations documented in receptor-binding domain (RBD) spike protein increases interaction between SARS-CoV-2 and its cellular receptor, angiotensin-converting enzyme (ACE2). Mutations can increase spread rate, severity, ability to evade either immune protective responses, monoclonal antibody treatments, or efficacy current licensed vaccines. This review aimed highlight functional classification used by World Health Organization (WHO), Phylogenetic Assignment Named Global Outbreak (PANGO), Initiative on Sharing All Influenza Data (GISAID), Nextstrain, an open-source project harness scientific public health potential pathogen genome data, chronological concern (VOCs) interest (VOIs), major findings related spread, are involved evasion host responses elicited prior infections protection induced vaccination.

Language: Английский

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The Biological Functions and Clinical Significance of SARS-CoV-2 Variants of Corcern

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: May 20, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve, emerging novel variants with spike protein mutations. Although most mutations emerged in the SARS-CoV-2 genome are neutral or mildly deleterious, a small number of can affect virus phenotype that confers fitness advantage. These enhance viral replication, raise risk reinfection and blunt potency neutralizing antibodies triggered by previous infection vaccination. Since December 2020, has five quickly spreading strains, designated concern (VOCs), including Alpha (B.1.1.7) variant, Beta (B.1.351) Gamma (P.1) Delta (B.1.617.2) variant Omicron (B.1.1.529) variant. have high promotes cell entry through angiotensin-converting enzyme -2 (ACE2). Mutations arisen receptor binding domain (RBD) great due their potential evade vaccines. The United Kingdom second half 2020 spread globally acquired E484K mutation States. South Africa Brazil, respectively, additional at positions E484 K417 RBD. containing combination N501Y, E484K, K417N/T exhibit remarkably decreased sensitivity mediated vaccination infection. may result more severe disease than other do even convalescent individuals. India many countries States Kingdom. 8 protein, some which influence immune responses key antigenic regions In early November 2021, was first detected Botswana Africa. harbors 30 located within RBD, been associated increased transmissibility evasion after Additionally, contains 3 deletions one insertion protein. Recently, classified into three sublineages, BA.1, BA.2, BA.3, strikingly different genetic characteristics. BA.2 sublineage virological landscapes, such as transmissibility, pathogenicity resistance vaccine-induced immunity compared BA.1 BA.3 sublineages. RBD VOCs increase making infectious transmissible enable vaccine-elicited antibodies. Unfortunately, emergence tempered optimism regarding efficacy COVID-19 This review addresses biological clinical significance impact on existing

Language: Английский

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