ConvMut: A Web tool to analyze viral convergent mutations along phylogenies DOI Creative Commons
Anna Bernasconi,

Emma Fanfoni,

Tommaso Alfonsi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Convergent evolution in protein antigens is common across pathogens and has also been documented SARS-CoV-2; the most likely reason need to evade selective pressure exerted by previous infection- or vaccine-elicited immunity. There a pressing for tools that allow automated analysis of convergent mutations. In response this need, we developed ConvMut, tool identifying patterns recurrent mutations SARS-CoV-2 evolution. To end, exploited granular phylogenetic tree representation PANGO, allowing us observe what call deltas, i.e., groups are acquired on top immediately upstream nodes. Deltas comprise both amino acid substitutions deletions. ConvMut can perform individual identify single independently given subtree (starting from user-selected root). Such represented barplot be sorted frequency position filtered region interest. Lineages then gathered into clusters according their sets shared Finally, an interactive graph orders clusters, details changes each sublineage, allows evolutive path until selected lineage. Other unique paired with main functionality support complete analysis, such as nucleotide at residue subtree. We expect will facilitate design antiviral anti-Spike monoclonal antibodies Spike-based vaccines longer-lasting efficacy, minimizing development marketing failures.

Language: Английский

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Cyril Planchais

et al.

Pathogens and Immunity, Journal Year: 2024, Volume and Issue: 10(1), P. 1 - 11

Published: Sept. 30, 2024

First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized.

Language: Английский

Citations

9
Development of the TSR-based computational method to investigate spike and monoclonal antibody interactions DOI Creative Commons

Tarikul I. Milon,

Titli Sarkar,

Yixin Chen

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: March 19, 2025

Introduction Monoclonal antibody (mAb) drug treatments have proven effective in reducing COVID-19-related hospitalizations or fatalities, particularly among high-risk patients. Numerous experimental studies explored the structures of spike proteins and their complexes with ACE2 mAbs. These 3D provide crucial insights into interactions between mAb, forming a basis for development diagnostic tools therapeutics. However, field computational biology has faced substantial challenges due to lack methods precise protein structural comparisons accurate prediction molecular interactions. In our previous studies, we introduced Triangular Spatial Relationship (TSR)-based algorithm, which represents protein’s structure using vector integers (keys). earlier however, were limited individual proteins. Purpose This study introduces new extensions TSR-based enhancing its ability two molecules. We apply these gain mechanistic understanding - mAb Method expanded basic TSR method three novel ways: (1) keys encompassing all atoms, (2) cross molecules, (3) intra-residual amino acids. representation offers unique advantage by simplifying search similar substructures within datasets. Results The study’s key findings include: (i) effectively quantified interpreted conformational changes steric effects newly keys. (ii) Six clusters CDRH3 CDRL3 identified all-atom (iii) constructed TSR-STRSUM (TSR-STRucture SUbstitution Matrix), matrix that pairwise similarities acid structures, providing valuable applications sequence comparison. (iv) Intra-residual revealed distinct Tyr characterized specific triangle geometries. Conclusion presents an advanced approach not only quantifies interprets backbones, entire acids, but also facilitates induced binding across some instances, direct correlation functions was successfully established.

Language: Английский

Citations

0
Single Monoclonal Antibodies Should Not Be Used for Coronavirus Disease 2019 Therapy: A Call for Antiviral Stewardship DOI
Arturo Casadevall, Daniele Focosi, Liise-anne Pirofski

et al.

Clinical Infectious Diseases, Journal Year: 2024, Volume and Issue: 79(6), P. 1404 - 1407

Published: Aug. 8, 2024

Abstract The COVID-19 pandemic witnessed the greatest deployment of monoclonal antibody (mAb) therapies for an infectious disease, but all were defeated by SARS-CoV-2 evolution. As new mAbs are developed, disease community needs stewardship practices to reduce emergence resistance.

Language: Английский

Citations

4
Shielding the immunocompromised: COVID-19 prevention strategies for patients with primary and secondary immunodeficiencies DOI Creative Commons
G. Olivieri, Donato Amodio, Emma Concetta Manno

et al.

Vaccine, Journal Year: 2025, Volume and Issue: 51, P. 126853 - 126853

Published: Feb. 12, 2025

Language: Английский

Citations

0
Comparative Study of Ensitrelvir and Symptomatic Therapy in Healthcare Workers with Mild COVID-19: A Single Center Retrospective Analysis in Chiba, Japan. DOI
Jun Hirai, Yuki Hanai

Journal of Infection and Chemotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 102668 - 102668

Published: Feb. 1, 2025

Language: Английский

Citations

0
Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges DOI
Daniele Focosi, David J. Sullivan, Massimo Franchini

et al.

Expert Review of Anti-infective Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated

Language: Английский

Citations

0
citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform DOI Open Access
Joshua L. C. Wong, Julia Sanchez‐Garrido,

Jaie Rattle

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Abstract Existing technologies employed to generate antibodies against bacterial polysaccharides and proteins rely on the availability of purified or synthetic antigens. Here we present a genetics-based platform that utilises Citrobacter rodentium (CR), an enteric mouse pathogen, both produce complex heterologous polysaccharide protein antigens during natural infection. As proof concept, use lipopolysaccharide (O1), capsular (K2) type 3 fimbrial (T3F) expressed by WHO critical priority pathogen Klebsiella pneumoniae (KP). Following one infection cycle (28 days) CR induces specific IgG KPO1, KPK2 KPT3F. We demonstrate are functional in downstream applications including protection pathogenic KP challenge, serotyping biofilm inhibition. Whilst were used as prototypical examples, this modular is now readily adaptable diverse antigens, with basic science, public health therapeutic applications.

Language: Английский

Citations

0
Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis DOI Creative Commons
Pao-Yu Chen,

Tzong‐Yow Wu,

Jann‐Tay Wang

et al.

Journal of the Formosan Medical Association, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Replication Features of SARS-CoV-2 and Advantages of Targeting S Protein with Aptamers to Block Viral Entry DOI Creative Commons
Jun Zheng,

Qiuxia Pang,

Zhaoying Fu

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Language: Английский

Citations

0
Considerations for the development of monoclonal antibodies to address new viral variants in COVID-19 DOI
Arturo Casadevall, Scott A. McConnell, Daniele Focosi

et al.

Expert Opinion on Biological Therapy, Journal Year: 2024, Volume and Issue: 24(8), P. 787 - 797

Published: Aug. 1, 2024

Monoclonal antibody (mAb) therapies proved safe and effective in preventing progression of COVID-19 to hospitalization, but most were eventually defeated by continued viral evolution. mAb combinations those mAbs that deliberatively selected target conserved regions the SARS-CoV-2 spike protein more resilient escape variants as evident longer clinical useful lives.

Language: Английский

Citations

3