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

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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

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 121, n. 13, p. 10-pg., 2024-03-26.

Abstract

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. (AU)

• FAPESP's process: 13/07296-2 - CDMF - Center for the Development of Functional Materials
• Grantee: Elson Longo da Silva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/15147-4 - Computational study of thermodynamic association of self­-assembled systems
• Grantee: André Farias de Moura
• Support Opportunities: Regular Research Grants