Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2264 - 2264

Published: Jan. 23, 2023

The first 2 years of the COVID-19 pandemic were mainly characterized by recurrent mutations SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 emerging independently across different variants concern (Alpha, Beta, Gamma, Delta). Such homoplasy is a marker convergent evolution. Since Spring 2022 third year pandemic, with advent Omicron its sublineages, evolution has led to observation lineages acquiring an additional group amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, S494. Mutations these have become increasingly prevalent during Summer Autumn 2022, combinations showing increased fitness. most likely reason for this convergence selective pressure exerted previous infection- or vaccine-elicited immunity. accelerated caused failure all anti-Spike monoclonal antibodies, including bebtelovimab cilgavimab. While we are learning how fast coronaviruses can mutate recombine, should reconsider opportunities economically sustainable escape-proof combination therapies, refocus antibody-mediated therapeutic efforts on polyclonal preparations that less allow viral immune escape.

Language: Английский

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Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 944 - 944

Published: April 10, 2023

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of has given rise to multiple variants varying pathogenicity transmissibility, such as Delta Omicron variants. Individuals advanced age or underlying comorbidities, including hypertension, diabetes cardiovascular diseases, are at higher risk increased disease severity. Hence, this resulted in an urgent need for development better therapeutic preventive approaches. This review describes origin human coronaviruses, particularly well sub-variants. Risk factors that contribute severity implications co-infections also considered. In addition, various antiviral strategies against COVID-19, novel repurposed drugs targeting viral host proteins, immunotherapeutic strategies, discussed. We critically evaluate current emerging vaccines their efficacy, immune evasion new impact on diagnostic testing examined. Collectively, global research public health authorities, along all sectors society, prepare upcoming future coronavirus outbreaks.

Language: Английский

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A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19)

Antibodies, Journal Year: 2023, Volume and Issue: 12(1), P. 5 - 5

Published: Jan. 11, 2023

Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies’ efficacy and long-term viability. Studies reported several antibodies, that received authorization COVID-19 treatment, not effective against new or subvariants SARS-CoV-2, hence their distribution has to be paused. Here, authors reviewed status currently available monoclonal potential as therapeutic agent, challenges ahead. To address issues, presented general information on how work SARS-CoV-2. The then focus have been deployed current status, well evidence supporting an early intervention Lastly, discussed some leading obstacles hinder development administration

Language: Английский

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An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Clinical Microbiology and Infection, Journal Year: 2024, Volume and Issue: 30(8), P. 999 - 1006

Published: April 24, 2024

Language: Английский

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Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience

Viruses, Journal Year: 2022, Volume and Issue: 15(1), P. 118 - 118

Published: Dec. 30, 2022

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk adverse outcomes. This has driven largely expanding field monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), long-acting antibody combination that inhibits attachment SARS-CoV-2 spike protein to surface cells, proved promising reducing incidence symptomatic or death high-risk individuals without major events when given as prophylaxis, well early treatment. Real-world data confirm combination’s prophylaxis efficacy lowering incidence, hospitalization, mortality associated solid organ transplant recipients, immune-mediated inflammatory diseases hematological malignancies, B-cell-depleting therapies. Data suggest difference neutralization efficiency between subtypes favor BA.2 over BA.1. In treating COVID-19, AZD7442 showed significant reduction severe cases course disease, within 5 days symptom onset, being events, it is addition standard care. The possibility development spike-protein mutations resist antibodies been reported; therefore, increased vigilance required view evolving variants. may be powerful ally preventing individuals. Further research include more groups assess concerns limiting its use, along evolutionary trajectory.

Language: Английский

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SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments

Vaccines, Journal Year: 2022, Volume and Issue: 10(12), P. 2145 - 2145

Published: Dec. 14, 2022

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines drugs end pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs a novel lineage of beta coronaviruses in subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, are effective treatments beneficial preventing infection. Numerous studies already been conducted using genome sequence comparison with that other SARS-like viruses, numerous treatments/prevention measures currently undergoing or undergone clinical trials. We summarize these depth hopes highlighting some key details will help us better understand viral origin, epidemiology, virus.

Language: Английский

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Ruxolitinib treatment in myelofibrosis and polycythemia vera causes suboptimal humoral immune response following standard and booster vaccination with BNT162b2 mRNA COVID-19 vaccine

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 14, 2023

Patients affected by myelofibrosis (MF) or polycythemia vera (PV) and treated with ruxolitinib are at high risk for severe coronavirus disease 2019. Now a vaccine against the virus SARS-CoV-2, which is responsible this disease, available. However, sensitivity to vaccines usually lower in these patients. Moreover, fragile patients were not included large trials investigating efficacy of vaccines. Thus, little known about approach group In prospective single-center study, we evaluated 43 (30 MF 13 PV) receiving as treatment their myeloproliferative disease. We measured anti-spike anti-nucleocapsid IgG SARS-CoV2 15-30 days after second third BNT162b2 mRNA booster dose. showed an impaired antibody response complete vaccination (2 doses), 32.5% did develop any response. After dose Comirnaty, results slightly improved, 80% produced antibodies above threshold positivity. quantity was well below that reached than those reported healthy individuals. PV elicited better MF. different strategies should be considered high-risk

Language: Английский

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The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 25, 2023

Over three years’ pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and subvariants have emerged successively, outcompeted earlier become predominant. The sequential emergence reflects the evolutionary process mutation-selection-adaption severe acute respiratory syndrome 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in spike protein causes altered viral antigenicity, transmissibility, pathogenicity SARS-CoV-2. Early pandemic, D614G mutation conferred virus with advantages over previous increased it also laid a conservative background for subsequent substantial mutations. role genomic recombination evolution SARS-CoV-2 raised increasing concern occurrence recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, XBB.1.16 late phase pandemic. Co-circulation different co-infection immunocompromised patients accelerate recombinants. Surveillance variations, particularly recombination, is essential to identify ongoing changes genome antigenic epitopes thus leads development new vaccine strategies interventions.

Language: Английский

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Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE)

Open Forum Infectious Diseases, Journal Year: 2023, Volume and Issue: 10(7)

Published: June 13, 2023

Abstract Background The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial adintrevimab, an extended–half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) symptomatic COVID-19. Methods Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive single 300-mg intramuscular injection adintrevimab or placebo. Primary efficacy end points reverse transcription polymerase chain reaction (RT-PCR)–confirmed COVID-19 through day 28 the PEP cohort (RT-PCR-negative at baseline) month 3 PrEP seronegative among before emergence severe acute respiratory syndrome 2 Omicron variant (November 30, 2021). Safety assessed 6 months. Results Between April 27, 2021, January 11, 2022, 2582 randomized. In primary analysis, RT-PCR-confirmed occurred 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab- placebo-treated participants, respectively (74.9% relative risk reduction [RRR]; standardized difference, −5.0%; 95% CI, −8.87% −1.08%; P = .0123) 12/752 (1.6%) 40/728 (5.5%) (71.0% RRR; −3.9%; −5.75% −2.01%; < .0001). prespecified exploratory analysis 428 after Omicron, reduced by 40.6% (standardized difference −8.4%; −15.35% −1.46%; nominal .0177) Adintrevimab well tolerated, with no serious drug-related adverse events reported. Conclusions A provided prophylactic against due susceptible variants without safety concerns. Clinical registration. NCT04859517.

Language: Английский

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Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 17, 2025

Immunocompromised patients struggle to adequately clear viral infections, offering the virus opportunity adapt immune system in host. Here we present a case study of patient undergoing allogeneic hematopoietic stem cell transplantation with 521-day follow-up SARS-CoV-2 infection BF.7.21 variant. Virus samples from five time points were submitted whole genome sequencing. Between first detection and its clearance, patient's population acquired 34 amino acid substitutions 8 deletions coding regions. With 11 receptor binding domain virus' spike protein, 15 times more abundant than expected for random distribution this highly functional region. Amongst them S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, S:E484V at positions that are notorious their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.

Language: Английский

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