tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Mar 26;121(13):e2310469121.
doi: 10.1073/pnas.2310469121. Epub 2024 Mar 19. Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants
Rui Gao[SUP] #[/SUP][SUP] 1 2 [/SUP], Xinxin Xu[SUP] #[/SUP][SUP] 1 2 [/SUP], Prashant Kumar[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Ye Liu[SUP] 6 [/SUP], Hongyu Zhang[SUP] 1 2 [/SUP], Xiao Guo[SUP] 1 2 [/SUP], Maozhong Sun[SUP] 1 2 [/SUP], Felippe Mariano Colombari[SUP] 7 [/SUP], André F de Moura[SUP] 8 [/SUP], Changlong Hao[SUP] 1 2 [/SUP], Jessica Ma[SUP] 3 4 5 9 [/SUP], Emine Sumeyra Turali Emre[SUP] 3 4 5 9 [/SUP], Minjeong Cha[SUP] 3 4 5 [/SUP], Liguang Xu[SUP] 1 2 [/SUP], Hua Kuang[SUP] 1 2 [/SUP], Nicholas A Kotov[SUP] 3 4 5 9 [/SUP], Chuanlai Xu[SUP] 1 2 [/SUP]
Affiliations
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 (IC[SUB]50[/SUB]) 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 IC[SUB]50[/SUB] 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.
Keywords: biomimetic; capsids; chiral nanoparticles; self-assembly; supraparticles.
. 2024 Mar 26;121(13):e2310469121.
doi: 10.1073/pnas.2310469121. Epub 2024 Mar 19. Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants
Rui Gao[SUP] #[/SUP][SUP] 1 2 [/SUP], Xinxin Xu[SUP] #[/SUP][SUP] 1 2 [/SUP], Prashant Kumar[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Ye Liu[SUP] 6 [/SUP], Hongyu Zhang[SUP] 1 2 [/SUP], Xiao Guo[SUP] 1 2 [/SUP], Maozhong Sun[SUP] 1 2 [/SUP], Felippe Mariano Colombari[SUP] 7 [/SUP], André F de Moura[SUP] 8 [/SUP], Changlong Hao[SUP] 1 2 [/SUP], Jessica Ma[SUP] 3 4 5 9 [/SUP], Emine Sumeyra Turali Emre[SUP] 3 4 5 9 [/SUP], Minjeong Cha[SUP] 3 4 5 [/SUP], Liguang Xu[SUP] 1 2 [/SUP], Hua Kuang[SUP] 1 2 [/SUP], Nicholas A Kotov[SUP] 3 4 5 9 [/SUP], Chuanlai Xu[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38502692
- DOI: 10.1073/pnas.2310469121
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 (IC[SUB]50[/SUB]) 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 IC[SUB]50[/SUB] 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.
Keywords: biomimetic; capsids; chiral nanoparticles; self-assembly; supraparticles.