Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2.

Autor: Lee, Dongtak, Jung, Hyo Gi, Park, Dongsung, Bang, Junho, Cheong, Da Yeon, Jang, Jae Won, Kim, Yonghwan, Lee, Seungmin, Lee, Sang Won, Lee, Gyudo, Kim, Yeon Ho, Hong, Ji Hye, Hwang, Kyo Seon, Lee, Jeong Hoon, Yoon, Dae Sung
Zdroj: Nature Communications; 3/7/2024, Vol. 15 Issue 1, p1-13, 13p
Abstrakt: 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 (Mpro) 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 Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.The main protease (Mpro) plays a crucial role in the replication of SARS-CoV-2, thereby making it an attractive target for COVID-19 treatment. Here, the authors develop a colorimetric screening platform for discovering Mpro inhibitors using engineered amyloid peptide-based nanocomplexes. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index