Abstract
The ability of pathogens to develop drug resistance is a global health challenge. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an urgent need wherein several variants of concern resist neutralization by monoclonal antibody (mAb) therapies and vaccine-induced sera. Decoy nanoparticles-cell-mimicking particles that bind and inhibit virions-are an emerging class of therapeutics that may overcome such drug resistance challenges. To date, quantitative understanding as to how design features impact performance of these therapeutics is lacking. To address this gap, this study presents a systematic, comparative evaluation of various biologically derived nanoscale vesicles, which may be particularly well suited to sustained or repeated administration in the clinic due to low toxicity, and investigates their potential to inhibit multiple classes of model SARS-CoV-2 virions. A key finding is that such particles exhibit potent antiviral efficacy across multiple manufacturing methods, vesicle subclasses, and virus-decoy binding affinities. In addition, these cell-mimicking vesicles effectively inhibit model SARS-CoV-2 variants that evade mAbs and recombinant protein-based decoy inhibitors. This study provides a foundation of knowledge that may guide the design of decoy nanoparticle inhibitors for SARS-CoV-2 and other viral infections.
Keywords: ACE2; SARS-CoV-2; decoys; extracellular vesicles; nanovesicles.
【저자키워드】 SARS-CoV-2, ACE2, Extracellular vesicles, decoys, nanovesicles., 【초록키워드】 severe acute respiratory syndrome coronavirus 2, coronavirus, therapy, Therapeutics, neutralization, knowledge, monoclonal antibody, SARS-CoV-2 variant, Toxicity, Extracellular vesicles, severe acute respiratory syndrome Coronavirus, inhibitors, viral infections, Particle, Health, Viral, pathogen, sera, antiviral efficacy, Pathogens, drug resistance, respiratory, inhibitor, Quantitative, mAbs, mAb, administration, decoy, Recombinant protein, binding affinities, acute respiratory syndrome, acute respiratory syndrome coronavirus, clinic, foundation, several variants, SARS-CoV-2 virions, virions, vesicles, repeated, Vesicle, feature, Extracellular, develop, addition, inhibit, provide, overcome, evade, sustained, several variant, 【제목키워드】 Engineering, principle,