Activity of SARS-CoV-2 protease 3CLpro on collagen fibrils, fibrin, alpha-synuclein, and amyloid-beta
SUSANTA K SARKAR
Project Goals and Description:
The pandemic caused by SARS-CoV-2 has caused many infections and deaths with far-reaching global economic and societal implications. One of the drug targets among coronaviruses is a protease called Mpro or 3CLpro. The current pandemic-causing virus SARS-CoV-2 also produces 3CLpro in infected human cells. The protease activity of 3CLpro is essential to produce functional proteins necessary for coronavirus propagation. Preliminary results suggest that 3CLpro can degrade native type-1 collagen, the primary component of the extracellular matrix providing a scaffold for cells. The collagenolytic activity of 3CLpro is significant because there are not many enzymes capable of degrading native type-1 collagen. Human matrix metalloprotease-1 (MMP1) can degrade collagen and shows similar broad-spectrum activity. Despite having only 33% sequence similarity, both 3CLpro and MMP1 have two parts connected by a linker and have allosteric communications (correlations between two distant points). This proposal quantifies 3CLpro activity on type-1 collagen, alpha-synuclein, fibrin(ogen), and amyloid-beta peptide because MMP1 shows activity on these substrates. If successful, this proposal might lead to an avenue for COVID-19 treatment and establish 3CLpro as a viral collagenase.
Team members must collaborate and focus on specific tasks with the overall picture in mind.
Grand Challenge: Advance health informatics.
TIME COMMITMENT (HRS/WK)
Hands-on molecular biology experiment, computation, and data analysis.
Student will work with senior members of the group and attend weekly group meetings.
PREFERRED STUDENT STATUS