Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 449 - 475

Опубликована: Апрель 19, 2023

Язык: Английский

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Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Окт. 20, 2022

Abstract Continued evolution of SARS-CoV-2 has led to the emergence several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine neutralization resistance these as well their ancestral BA.4/5, BA.2.75 D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, BA.5-wave patients. We found enhanced in all especially BQ.1 BQ.1.1 subvariants driven by a key N460K mutation, lesser extent, R346T K444T mutations, BA.2.75.2 subvariant largely its F486S mutation. The also exhibited fusogenicity S processing dictated Interestingly, saw an enhancement mutation reduction D1199N processing, resulting minimal overall change. Molecular modelling revealed mechanisms receptor-binding non-receptor binding monoclonal antibody-mediated immune evasion R346T, K444T, mutations. Altogether, findings shed light on concerning newly emerging subvariants.

Язык: Английский

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Nanotechnology-based mRNA vaccines

Nature Reviews Methods Primers, Год журнала: 2023, Номер 3(1)

Опубликована: Авг. 17, 2023

Язык: Английский

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Antiviral neutralizing antibodies: from in vitro to in vivo activity

Nature reviews. Immunology, Год журнала: 2023, Номер 23(11), С. 720 - 734

Опубликована: Апрель 17, 2023

Язык: Английский

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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein

Science Immunology, Год журнала: 2023, Номер 8(81)

Опубликована: Янв. 26, 2023

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy vaccines and antiviral monoclonal antibodies. Continued development immunotherapies vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions virus spike glycoprotein are both functionally relevant averse change, we identified human neutralizing antibodies highly conserved epitopes. Antibody fp.006 binds fusion peptide cross-reacts against coronaviruses four genera, including nine coronaviruses, through recognition motif includes S2' site proteolytic cleavage. hr2.016 targets stem helix neutralizes SARS-CoV-2 variants. sd1.040 subdomain 1, synergizes with rbd.042 for neutralization, and, similar hr2.016, protects mice expressing angiotensin-converting enzyme infection when present as bispecific antibody. Thus, discovery reveals donor-derived cross-reactive Orthocoronavirinae,

Язык: Английский

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ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines

Cell, Год журнала: 2023, Номер 186(11), С. 2380 - 2391.e9

Опубликована: Апрель 21, 2023

Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain levels. We present a natural infection-mimicking technology that combines features of mRNA- protein nanoparticle-based through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins induce budding from cells. Purified spike-EABR eVLPs presented densely arrayed spikes elicited potent in mice. Two immunizations with mRNA-LNP CD8+ T cell superior neutralizing original variant compared conventional spike-encoding purified eVLPs, improving titers >10-fold 3 months post-boost. Thus, EABR enhances potency breadth vaccine-induced antigen presentation on surfaces enabling longer-lasting protection other viruses.

Язык: Английский

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

Protein & Cell, Год журнала: 2024, Номер 15(6), С. 403 - 418

Опубликована: Март 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Язык: Английский

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Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants

Viruses, Год журнала: 2024, Номер 16(2), С. 217 - 217

Опубликована: Янв. 31, 2024

Among the anti-Spike monoclonal antibodies (mAbs), S-309 derivative sotrovimab was most successful in having longest temporal window of clinical use, showing a high degree resiliency to SARS-CoV-2 evolution interrupted only by appearance BA.2.86* variant interest (VOI). This success undoubtedly reflects rational selection target highly conserved epitope coronavirus Spike proteins. We review here efficacy against different variants outpatients and inpatients, discussing both randomized controlled trials real-world evidence. Although it could not be anticipated at time its development introduction, sotrovimab's use immunocompromised individuals who harbor large populations viruses created conditions for eventual demise, as antibody viral led withdrawal due inefficacy later lineages. Despite this, based on observational data, some authorities have continued promote sotrovimab, but lack binding newer strongly argues futility use. The story highlights power modern biomedical science generate novel therapeutics while also providing cautionary tale need devise strategies minimize emergence resistance antibody-based therapeutics.

Язык: Английский

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COVID-19 drug discovery and treatment options

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(7), С. 391 - 407

Опубликована: Апрель 15, 2024

Язык: Английский

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Mucosal immune response in biology, disease prevention and treatment

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Язык: Английский

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