Clinical and laboratory considerations: determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19 DOI Creative Commons
Stefan Holdenrieder, Carlos Eduardo dos Santos Ferreira, Jacques Izopet

et al.

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 28, 2023

Much of the global population now has some level adaptive immunity to SARS-CoV-2 induced by exposure virus (natural infection), vaccination, or a combination both (hybrid immunity). Key questions that subsequently arise relate duration and protection an individual might expect based on their infection vaccination history. A multi-component composite correlate risk (CoR) could inform individuals stakeholders about aid decision making. This perspective evaluates various elements need be accommodated in development antibody-based CoR for reinfection with severe COVID-19, including variation dose, transmission route, viral genetic variation, patient factors, status. We provide overview antibody dynamics exploration specifics testing. further discuss anti-SARS-CoV-2 immunoassays, sample matrices, testing formats, frequency sampling optimal time point such sampling. While is challenging, we our recommendations each these key areas highlight require work undertaken.

Language: Английский

SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice DOI Creative Commons
María F. Pavan, Marina Bok, Rafael Betanzos San Juan

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 185 - 185

Published: Jan. 25, 2024

Since the beginning of COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines combat disease. In this work, we developed llama-derived nanobodies (Nbs) directed against receptor binding domain (RBD) other domains Spike (S) protein SARS-CoV-2. Most Nbs with neutralizing properties were RBD able block S-2P/ACE2 interaction. Three recognized N-terminal (NTD) S-2P protein. Intranasal administration induced protection ranging from 40% 80% after challenge WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, was associated reduction virus replication nasal turbinates load brain. Employing pseudovirus neutralization assays, identified capacity Alpha, Beta, Delta, Omicron variants, including Nb capable all variants tested. Furthermore, cocktails different performed better than individual at two (B.1.529 BA.2). Altogether, data suggest potential SARS-CoV-2 specific for intranasal treatment encephalitis.

Language: Английский

Citations

5
Development of potent pan‐coronavirus fusion inhibitors with a new design strategy DOI Creative Commons
Yuanmei Zhu,

Zhongcai Gao,

Xiaoli Feng

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 28, 2024

Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one the top priorities, especially in cases emergence mutant viruses inability current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, report its design strategy preclinical data. First, surprisingly found that IPB29 with rigid linker between peptide sequence lipid molecule had greatly improved α‐helical structure antiviral activity. Second, potently inhibited large panel SARS‐CoV‐2 variants including previously circulating viruses, such as Omicron XBB.5.1 EG.5.1. Third, could also cross‐neutralize bat‐ pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, PCoV‐GX) other human (SARS‐CoV, MERS‐CoV, HCoV‐NL63, HCoV‐229E). Fourth, administrated an inhalation solution (IPB29‐IS) Syrian hamsters exhibited high therapeutic preventive efficacies Delta or variant. Fifth, pharmacokinetic profiles safety pharmacology IPB29‐IS were extensively characterized, providing data support evaluation humans. conclusion, our studies demonstrated for fusion inhibitors offered ideal drug candidate coronaviruses.

Language: Английский

Citations

4
Functional Activity and Binding Specificity of Small Ankyrin Repeat Proteins Called Ankyrons Against SARS-CoV-2 Variants DOI Creative Commons
Yun-Jong Park, Wojciech Jankowski,

Nicholas C. Hurst

et al.

The AAPS Journal, Journal Year: 2025, Volume and Issue: 27(2)

Published: March 11, 2025

Abstract Effective management of COVID-19 requires clinical tools to treat the disease in addition preventive vaccines. Several recombinant mAbs and their cocktails have been developed but these limitations. Here, we evaluate small ankyrin repeat proteins called Ankyrons that were generated bind with high affinity SARS-CoV-2 virus. are comprised repetitions a structural module. Each module consists β-turn followed by two antiparallel α-helices. The Ankyrons™ directly selected vitro from highly diverse library around trillion clones ribosome display like antibodies can almost any target. We assessed against wild-type Delta (B.1.617.2) Omicron (BA.1) variants binding assay. determined all specific they did not MERS. While bound variant against, some also showed cross-reactivity three variants. Binding assays useful for screening analytes do provide information about effectiveness. Therefore, used pseudovirus-based neutralization assay show five evaluated neutralized strains SARS-CoV-2. provided workflow evaluation novel viral This suggests could be rapidly developing new research studying other emerging infectious diseases optional further potential into diagnostic even therapeutic applications. Graphical

Language: Английский

Citations

0
Computational Design and Evaluation of Peptides to Target SARS-CoV-2 Spike–ACE2 Interaction DOI Creative Commons

Saja Almabhouh,

Erika Cecon, Florence Basubas

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(8), P. 1750 - 1750

Published: April 14, 2025

The receptor-binding domain (RBD) of SARS-CoV-2 spike protein is responsible for the recognition Angiotensin-Converting Enzyme 2 (ACE2) receptor in human cells and, thus, plays a critical role viral infection. therapeutic value targeting this interaction has been proven by sizable body research investigating antibodies, small proteins, aptamers, and peptides. This study presents novel peptide that impinges between RBD ACE2. Starting from very large pool structurally designed peptides extracted our database, PepI-Covid19, diverse set were studied using molecular dynamics simulations. Ten most promising chemically synthesized validated both vitro cell-based assay. Our results indicate one (PEP10) exhibited highest disruption RBD/ACE2 complex, effectively blocking binding two molecules consequently inhibiting spike-mediated cell entry viruses pseudotyped with D614G, Delta, Omicron variants. PEP10 can potentially serve as scaffold be further optimized improved affinity efficacy.

Language: Английский

Citations

0
The brief overview, antivirus and anti-SARS-CoV-2 activity, quantitative methods, and pharmacokinetics of cepharanthine: a potential small-molecule drug against COVID-19 DOI Creative Commons
Binbin Xia, Zheng Li, Yali Li

et al.

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

Published: July 31, 2023

To effectively respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an increasing number of researchers are focusing on the antiviral activity cepharanthine (CEP), which is a clinically approved drug being used for over 70 years. This review aims provide brief overview CEP and summarize its recent findings in quantitative analysis, pharmacokinetics, therapeutic potential, mechanism anti-SARS-CoV-2 activity. Given remarkable capacity against SARS-CoV-2 infection vitro vivo, with primary target organ lungs, good pharmacokinetic profile; mature stable manufacturing technique; advantages safety, effectiveness, accessibility, has become promising candidate treating COVID-19 despite old drug.

Language: Английский

Citations

6
A Multi-Faceted Binding Assessment of Aptamers Targeting the SARS-CoV-2 Spike Protein DOI Open Access
Laia Civit, Nima Moradzadeh, Anna Jończyk

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4642 - 4642

Published: April 24, 2024

The COVID-19 pandemic has underscored the critical need for advancement of diagnostic and therapeutic platforms. These platforms rely on rapid development molecular binders that should facilitate surveillance swift intervention against viral infections. In this study, we have evaluated by three independent research groups binding characteristics various published RNA DNA aptamers targeting spike protein SARS-CoV-2 virus. For comparative analysis, employed different techniques such as biolayer interferometry (BLI), enzyme-linked oligonucleotide assay (ELONA), flow cytometry. Our data show discrepancies in reported specificity affinity among several underline importance standardized methods, impact biophysical techniques, controls used aptamer characterization. We expect our results to contribute selection application suitable detection SARS-CoV-2.

Language: Английский

Citations

1
In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2 DOI Creative Commons
Dora Buzas,

Adrian H Bunzel,

Oskar Staufer

et al.

Antibody Therapeutics, Journal Year: 2023, Volume and Issue: 6(4), P. 277 - 297

Published: Oct. 1, 2023

Abstract Background Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches accelerate development of reagents against infectious pathogens. Methods Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection vivo immunization design, produce validate nature-inspired nanoparticle-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Our resulted two innovations: (i) thermostable nasal vaccine called ADDoCoV, displaying multiple copies SARS-CoV-2 receptor binding motif derived epitope (ii) multivalent nanoparticle superbinder, Gigabody, including immune-evasive variants concern (VOCs). In generated neutralizing nanobodies electron cryo-microscopy established authenticity accessibility epitopes displayed by ADDoCoV. Gigabody comprising multimerized prevented virion attachment picomolar EC50. Vaccinating mice antibodies cross-reacting VOCs Delta Omicron. Conclusion study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use active passive provides blueprint crafting combat viral infections.

Language: Английский

Citations

3
Navigating Immune Landscapes: Insights From A Prospective Study DOI
Izzatul Aliaa Badaruddin, Zulhabri Othman, Wan Muhammad Azfar Wan Shuaib

et al.

Asia Pacific Journal of Public Health, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Language: Английский

Citations

0
Functional Activity and Binding Specificity of small Ankyron Repeat Proteins against SARS-CoV-2 variants DOI Creative Commons
Yun-Jong Park, Wojciech Jankowski,

Nicholas C. Hurst

et al.

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

Published: Oct. 11, 2024

Effective management of COVID-19 requires clinical tools to treat the disease in addition preventive vaccines. Several recombinant mAbs and their cocktails have been developed but these limitations. Here, we evaluate small ankyrin repeat proteins called Ankyrons that were generated bind with high affinity SARS-CoV-2 virus. are comprised repetitions a structural module. Each module consists beta-turn followed by two antiparallel alpha-helices. The directly selected vitro from highly diverse library around trillion clones ribosome display like antibodies can almost any target. We assessed against wild-type Delta Omicron variants binding assay. determined all specific they did not MERS, related coronavirus. While bound variant against, some also showed cross-reactivity three variants. Binding assays useful for screening analytes do provide information about effectiveness. Therefore, used pseudovirus-based neutralization assay show five evaluated neutralized strains SARS-CoV-2. provided workflow evaluation novel viral This suggests could be rapidly developing new research studying other emerging infectious diseases optional further potential into diagnostic even therapeutic applications.

Language: Английский

Citations

0
AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors DOI Creative Commons
Ioannis Gkekas, Sotirios Katsamakas, Stelios K. Mylonas

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(22), P. 8562 - 8585

Published: Nov. 13, 2024

Coronavirus disease 2019 (COVID-19) is caused by a new, highly pathogenic severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects human cells through its transmembrane spike (S) glycoprotein. The receptor-binding domain (RBD) of the S protein interacts with angiotensin-converting enzyme II (ACE2) receptor host cells. Therefore, pharmacological targeting this interaction might prevent infection or spread virus. Here, we performed virtual screening to identify small molecules block S-ACE2 interaction. Large compound libraries were filtered for drug-like properties, promiscuity and protein-protein interaction-targeting ability based on their ADME-Tox descriptors also exclude pan-assay interfering compounds. A properly designed AI-based pipeline was applied remaining compounds, comprising approximately 10% starting data sets, searching could bind RBD protein. All sorted according score, grouped structure postfiltered possible patterns ACE2 receptor, yielding 31 hits. These hit further tested inhibitory effect Spike RBD/ACE2 (19-615) Six compounds inhibited in dose-dependent manner while two them prevented from pseudotyped virus whose entry mediated SARS-CoV-2. Of benzimidazole derivative

Language: Английский

Citations

0