Tapered chiral nanoparticles as broad- spectrum thermally stable antivirals for SARS-CoV-2 variants

• 成果类型: Article
• 署名作者: Gao, Rui; Xu, Xinxin; Kumar, Prashant; Liu, Ye; Zhang, Hongyu; Guo, Xiao; Sun, Maozhong; Colombari, Felippe Mariano; Moura, Andre F. de; Hao, Changlong; Ma, Jessica; Emre, Emine Sumeyra Turali; Cha, Minjeong; Xu, Liguang; Kuang, Hua; Kotov, Nicholas A.; Xu, Chuanlai
• 署名单位: Jiangnan University; Jiangnan University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Institute of Medical Biology - CAMS; Universidade Federal de Sao Carlos; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13967
• DOI: 10.1073/pnas.2310469121
• 发表日期: 2024-03-26
• 关键词: inhibition; infection; MODEL

摘要

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad- spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. L- penicillamine- stabilized NPs with left-handed curved apexes display half- maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality- optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.