Researchers report the first inhibitor of SARS-CoV-2 Mac1 protein that inhibits replication of the virus

A recent study published in the Journal of Medicinal Chemistry unveils a potential breakthrough in combating COVID-19 and potentially other coronavirus infections.

Researchers from the University of Oulu, in collaboration with researchers at the University of Kansas and McDaniel College in Maryland, have identified a compound named "MDOLL-0229 " that effectively inhibits the replication of SARS-CoV-2, the virus behind COVID-19, by targeting a virus encoded Mac1 protein domain crucial for the virus's evasion of the immune system.

This compound, developed through joint efforts, particularly by researchers at the Protein and Structural Biology Research Unit at the Faculty of Biochemistry and Molecular Medicine and at the Research Unit of Sustainable Chemistry of the Faculty of Technology at the University of Oulu, showed promise in halting the ADP-ribose binding and hydrolysis activity of Mac1, a mechanism exploited by the virus during infection to evade immune response.

Lead author Lari Lehtiö from the University of Oulu highlighted the significance of this discovery, emphasizing the compound's efficacy in inhibiting coronavirus replication in cell models. Anthony Fehr, associate professor of molecular biosciences at KU, underscored the importance of Mac1 as a therapeutic target, indicating its potential for protecting against COVID-19 and other emerging coronaviruses.

The researchers emphasize the urgency of developing inhibitors targeting Mac1 across various coronaviruses, citing the looming threat of future pandemics. They also note the difficulty for coronaviruses to develop resistance against Mac1 targeted approaches, making it a promising avenue for therapy.

Moving forward, the researchers aim to validate these inhibitors through animal models, with the goal of developing effective treatments against multiple coronaviruses.

Link to the research article

Read also: Study reports new compound halting replication of COVID by targeting ‘Mac-1’ protein in cell models

Last updated: 8.5.2024