Cell, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Biomolecules, Journal Year: 2021, Volume and Issue: 11(7), P. 993 - 993
Published: July 6, 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of disease 2019 (COVID-19) pandemic, which has been a topic major concern for global human health. The challenge to restrain COVID-19 pandemic further compounded by emergence several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), show increased transmissibility resistance towards vaccines therapies. Importantly, there convincing evidence susceptibility infection among individuals with dysregulated immune response comorbidities. Herein, we provide comprehensive perspective regarding vulnerability in patients underlying medical We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) therapeutic (monoclonal antibodies, small molecules, plasma therapy, modalities designed curb pandemic. also detail, challenges posed different (VOC) identified across globe their effects on prophylactic interventions.
Language: Английский
Citations
169
Immunity, Journal Year: 2021, Volume and Issue: 54(6), P. 1304 - 1319.e9
Published: May 9, 2021
Language: Английский
Citations
147
Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: Sept. 22, 2021
SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four (C5, H3, C1, F2) engineered homotrimers pmolar affinity the receptor binding (RBD) of spike protein. Crystal structures show C5 H3 overlap ACE2 epitope, whilst C1 F2 bind different epitope. Cryo Electron Microscopy shows results in all down arrangement Spike neutralize Victoria strain, highly transmissible Alpha (B.1.1.7 first identified Kent, UK) strain also neutralizes Beta (B.1.35, South Africa). Administration C5-trimer via route showed potent therapeutic efficacy Syrian hamster model separately, prophylaxis. The molecule was similarly by intraperitoneal injection.
Language: Английский
Citations
131
Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107086 - 107086
Published: Jan. 29, 2024
The progress in human disease treatment can be greatly advanced through the implementation of nanomedicine. This approach involves targeted and cell-specific therapy, controlled drug release, personalized dosage forms, wearable delivery, companion diagnostics. By integrating cutting-edge technologies with delivery systems, greater precision achieved at tissue cellular levels use stimuli-responsive nanoparticles, development electrochemical sensor systems. targeting – by virtue nanotechnology allows for therapy to directed specifically affected tissues while reducing side effects on healthy tissues. As such, nanomedicine has potential transform conditions such as cancer, genetic diseases, chronic illnesses facilitating precise delivery. Additionally, forms devices offer ability tailor unique needs each patient, thereby increasing therapeutic effectiveness compliance. Companion diagnostics further enable efficient monitoring response, enabling customized adjustments plan. question whether all approaches outlined here are viable alternatives current treatments is also discussed. In general, application field biomedicine may provide a strong alternative existing several reasons. this review, we aim present evidence that, although early stages, fully merging technology innovative shows promise successful across various areas, including cancer or diseases.
Language: Английский
Citations
67
Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 195, P. 114726 - 114726
Published: Feb. 7, 2023
Language: Английский
Citations
43
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Jan. 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
Language: Английский
Citations
4
Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 111 - 111
Published: Jan. 12, 2025
Nanobodies have gained attention as potential therapeutic and diagnostic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their ability bind neutralize the virus. However, rapid, scalable, robust production of nanobodies SARS-CoV-2 remains a crucial challenge. In this study, we developed visual high-efficiency biomanufacturing method with Escherichia coli by fusing super-folder green fluorescent protein (sfGFP) N-terminus or C-terminus nanobody. Several receptor-binding domain (RBD)-specific spike (S) were secreted onto surface E. cells even into culture medium, including Fu2, ANTE, mNb6, MR3-MR3, n3113.1. The retained equal activity prior research, regardless whether sfGFP was removed. Since some bound different regions RBD, combined two improve affinity. Fu2-sfGFP-ANTE constructed be bispecific nanobody exhibited significantly higher affinity than Fu2 (35.0-fold), ANTE (7.3-fold), combination (3.3-fold). Notably, can normally medium outer membrane. novel system enhances efficiency expression streamlines downstream purification process, enabling large-scale, cost-effective production. addition, secreting on facilitates screening characterization antigen-binding clones.
Language: Английский
Citations
2
Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: Aug. 3, 2021
Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) SARS-CoV-2 spike promising therapeutics. However, it is unknown if Nbs broadly neutralize circulating variants. We found RBD highly resistant to concern (VOCs). High-resolution cryoelectron microscopy determination eight Nb-bound structures reveals multiple neutralizing epitopes clustered into three classes: Class I targets ACE2-binding sites disrupts host binding. II binds conserved retains activity VOCs RBDSARS-CoV. Cass III recognizes unique likely inaccessible antibodies. Systematic comparisons antibodies provided insights how achieve high-affinity activity. Structure-function analysis indicates a variety antiviral mechanisms. Our study may guide rational design pan-coronavirus vaccines
Language: Английский
Citations
94
Cell Reports, Journal Year: 2021, Volume and Issue: 37(3), P. 109869 - 109869
Published: Oct. 1, 2021
The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived alpaca immunized with the severe acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein (S); among them, three exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating variants. To improve their efficacy, various configurations of engineered. Nb15-NbH-Nb15, trimer constituted Nbs, is constructed to be bispecific human serum albumin (HSA) RBD SARS-CoV-2. Nb15-NbH-Nb15 exhibits single-digit ng/ml neutralization wild-type Delta variants long half-life in vivo. In addition, show that intranasal administration provides protection both prophylactic purposes infection transgenic hACE2 mice. candidate prevention treatment through administration.
Language: Английский
Citations
84
TURKISH JOURNAL OF MEDICAL SCIENCES, Journal Year: 2021, Volume and Issue: 51(SI-1), P. 3372 - 3390
Published: Aug. 15, 2021
Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning pandemic, and many them used COVID-19 despite preliminary or conflicting results clinical trials. We aimed to review summarize all current knowledge on antivirals COVID-19There are 2 main drug groups SARS-CoV-2: agents that target proteins RNA virus interfere with biological processes in host support virus. The include inhibitors viral entry into human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), supporting (plitidepsin, fluvoxamine, ivermectin), natural immunity (Interferons).When taking account available laboratory trials subject, antibodies seem be most at moment, high-titer convalescent plasma also could when administered during early phase disease. As lopinavir/ritonavir, were found ineffective RCTs, they should used. Additional studies needed define role remdesivir, interferons, ivermectin, proxulutamide, bromhexine, nitazoxanide, niclosamid COVID-19. Finally, waited learn whether newer such as plitidepsin AT-527
Language: Английский
Citations
78