Research

Life Sciences & Biotechnology

Title :

Development of non-covalent dual inhibitors against pan-coronavirus MPro and PLPro proteases: Addressing the drug resistance and preparation for the future

Area of research :

Life Sciences & Biotechnology

Focus area :

structural Biology

Principal Investigator :

Dr. Anthony Addlagatta, CsIR- Indian Institute of Chemical Technology, Hyderabad, secunderabad, Telangana

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

Human corona viruses (HCoVs) have been causing respiratory infections since the 1960s, but their pathogenicity was not considered until the emergence of severe acute respiratory syndrome coronavirus in 2002. MERs-CoV and sARs-CoV-2 were identified in 2012 and 2019, respectively, causing devastating consequences. Dual inhibitors of main protease (MPro) and papain-like protease (PLPro) can prevent viral replication and drug resistance due to mutations in the viral genome. A high-throughput study screened 1.8 million compounds, identifying six molecules as dual inhibitors of MPro and PLPro. These molecules, with a 2-chloroquinoline-based imine moiety, show better antiviral properties and are non-cytotoxic against several human cell lines. These molecules inhibit sARs-CoV-2 replication at below one micromolar concentration. The first study to develop non-covalent dual inhibitors against MPro and PLPro is ongoing, and the lead compounds identified may have equal affinity to enzymes from other corona viruses due to their conserved active sites. The researchers propose exploring these compounds against homologues proteases from other corona viruses, specifically from sARs-CoV-1 and MERs-CoV, and optimizing their efficacy without compromising cytotoxicity.

Co-PI:

Dr. srigiridhar Kotamraju, CsIR- Indian Institute ff Chemical Technology, Telangana, Hyderabad (500007)

Total Budget (INR):

67,99,080

Organizations involved