Drug resistance in viruses represents one of the major challenges of healthcare. As part of an effort to provide a treatment that avoids the possibility of drug resistance, we discovered a novel mechanism of action (MOA) and specific compounds to treat all nine human herpesviruses and animal herpesviruses.
The novel MOA targets the pressurized genome state in a viral capsid, “turns off” capsid pressure, and blocks viral genome ejection into a cell nucleus, preventing viral replication. This work serves as a proof-of-concept to demonstrate the feasibility of a new antiviral target—suppressing pressure-driven viral genome ejection—that is likely impervious to developing drug resistance.
This pivotal finding presents a platform for discovery of a new class of broad-spectrum treatments for herpesviruses and other viral infections with genome-pressure-dependent replication. A biophysical approach to antiviral treatment such as this is also a vital strategy to prevent the spread of emerging viruses where vaccine development is challenged by high mutation rates or other evasion mechanisms.
This work presents a proof-of-concept for anti-herpes treatment based on a novel mechanism of action that interferes with ejection of herpes genome into a host cell by perturbing the viral genome pressure inside the virus’ protein shell, termed a capsid. This interference stops viral infection. Targeting the pressurized DNA state inside a herpes capsid presents a platform for development of broad-spectrum treatments for all human–and animal herpesviruses that are not susceptible to mutation-based resistance development