tetano
Editor, Senior Moderator
Nat Commun
. 2024 Mar 7;15(1):2108.
doi: 10.1038/s41467-024-46296-7. Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2
Dongtak Lee[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Hyo Gi Jung[SUP] #[/SUP][SUP] 1 4 [/SUP], Dongsung Park[SUP] #[/SUP][SUP] 1 5 [/SUP], Junho Bang[SUP] 1 4 [/SUP], Da Yeon Cheong[SUP] 6 7 [/SUP], Jae Won Jang[SUP] 1 4 [/SUP], Yonghwan Kim[SUP] 1 4 [/SUP], Seungmin Lee[SUP] 1 8 [/SUP], Sang Won Lee[SUP] 1 9 [/SUP], Gyudo Lee[SUP] 6 7 [/SUP], Yeon Ho Kim[SUP] 1 4 [/SUP], Ji Hye Hong[SUP] 1 8 [/SUP], Kyo Seon Hwang[SUP] 10 [/SUP], Jeong Hoon Lee[SUP] 11 [/SUP], Dae Sung Yoon[SUP] 12 13 14 [/SUP]
Affiliations
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (M[SUP]pro[/SUP]) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo M[SUP]pro[/SUP]-inhibitor screening platform to evaluate the efficacies of M[SUP]pro[/SUP] inhibitors based on M[SUP]pro[/SUP] cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and M[SUP]pro[/SUP]-cleavage sequence, mimicking in vivo viral replication process mediated by M[SUP]pro[/SUP]. By measuring the proteolytic activity of M[SUP]pro[/SUP] and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of M[SUP]pro[/SUP] inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering M[SUP]pro[/SUP] inhibitors and may accelerate the development of therapeutics against COVID-19.
. 2024 Mar 7;15(1):2108.
doi: 10.1038/s41467-024-46296-7. Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2
Dongtak Lee[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Hyo Gi Jung[SUP] #[/SUP][SUP] 1 4 [/SUP], Dongsung Park[SUP] #[/SUP][SUP] 1 5 [/SUP], Junho Bang[SUP] 1 4 [/SUP], Da Yeon Cheong[SUP] 6 7 [/SUP], Jae Won Jang[SUP] 1 4 [/SUP], Yonghwan Kim[SUP] 1 4 [/SUP], Seungmin Lee[SUP] 1 8 [/SUP], Sang Won Lee[SUP] 1 9 [/SUP], Gyudo Lee[SUP] 6 7 [/SUP], Yeon Ho Kim[SUP] 1 4 [/SUP], Ji Hye Hong[SUP] 1 8 [/SUP], Kyo Seon Hwang[SUP] 10 [/SUP], Jeong Hoon Lee[SUP] 11 [/SUP], Dae Sung Yoon[SUP] 12 13 14 [/SUP]
Affiliations
- PMID: 38453923
- DOI: 10.1038/s41467-024-46296-7
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (M[SUP]pro[/SUP]) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo M[SUP]pro[/SUP]-inhibitor screening platform to evaluate the efficacies of M[SUP]pro[/SUP] inhibitors based on M[SUP]pro[/SUP] cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and M[SUP]pro[/SUP]-cleavage sequence, mimicking in vivo viral replication process mediated by M[SUP]pro[/SUP]. By measuring the proteolytic activity of M[SUP]pro[/SUP] and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of M[SUP]pro[/SUP] inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering M[SUP]pro[/SUP] inhibitors and may accelerate the development of therapeutics against COVID-19.