Periodic Reporting for period 1 - MeTIC (Methyltransferase inhibitors for treatment of COVID19)
Reporting period: 2022-06-01 to 2023-11-30
Recent pandemics and outbreaks, such as 2009 Influenza A, 2016 Zika, COVID-19 and 2022/3 Monkeypox, highlight the requirement for expansion of the clinical toolbox for monitoring and treating viral infectious diseases in addition to vaccines. Against this backdrop, our persistent inability to develop effective treatments for virus infections remains a glaring gap of clinical medicine. This deficiency not only hinders our ability to provide care to patients afflicted by viral diseases, but also exposes a critical vulnerability in our capacity to prepare and respond effectively to the existing and emerging viral threats.
Despite the remarkable diversity of viruses that cause human diseases, spanning 26 distinct evolutionary families, the host's innate immune responses exhibit a striking ability to mount effective antiviral defenses against each of them. It is particularly noteworthy that many of these act through modulation of cellular metabolic processes. However, our comprehension of the metabolic constraints governing virus infections remains exceedingly sparse. Specifically, we lack knowledge regarding the metabolites essential for facilitating virus replication and their potential depletion as a limiting factor.
Project METIC evaluated antiviral strategies centered on broad-spectrum inhibition of viral methyltransferases both in terms of technical feasibility as well as provided fundamental supporting evidence for intellectual property protection. These are collectively required to further the preclinical pursuit of these antivirals and facilitate their potential clinical exploration.
Despite the remarkable diversity of viruses that cause human diseases, spanning 26 distinct evolutionary families, the host's innate immune responses exhibit a striking ability to mount effective antiviral defenses against each of them. It is particularly noteworthy that many of these act through modulation of cellular metabolic processes. However, our comprehension of the metabolic constraints governing virus infections remains exceedingly sparse. Specifically, we lack knowledge regarding the metabolites essential for facilitating virus replication and their potential depletion as a limiting factor.
Project METIC evaluated antiviral strategies centered on broad-spectrum inhibition of viral methyltransferases both in terms of technical feasibility as well as provided fundamental supporting evidence for intellectual property protection. These are collectively required to further the preclinical pursuit of these antivirals and facilitate their potential clinical exploration.
Project METIC evaluated viral methyltransferase inhibitors in state of the art in vivo and primary cell infection models, both in terms of efficacy as well as in terms of beneficial or detrimental collateral activities. We explored additional routes of administration and as proof of concept validated the efficacy of an alternative formulation in vitro. Due to ongoing patenting process, specifics of the performed work can not be made publically available at this time.
Mechanistic investigations of antiviral strategies involving inhibition of viral methyltransferases undertaken as part of the project METIC allowed us to further their preclinical pursuit.