SWITZERLAND, SATURDAY, 7 MARCH 2020 5:15 PM CET
Demiurge is responding to the global outbreak of the 2019 novel coronavirus (COVID-19) through the appropriate use of our AI platform that can make accurate drug discoveries for diseases with limited available clinical data.
Based on the deep analyses of published studies, clinical data and case reports on COVID-19 and our previously announced four AI-based discoveries for COVID-19, we hereby officially announce the 5th AI-based discovery of the complete aetiology of COVID-19 as below:
Viral survival strategy: COVID-19 adopts a unique unbiased survival strategy of balancing viral replication with viral spread, in stark contrast to other viruses that typically trade off one against the other. For example, MERS coronavirus adopts a survival strategy that prioritizes viral replication over viral spread, whereas influenza viruses adopt a survival strategy that prioritizes viral spread over viral replication.
Viral infection stages: COVID-19’s course of infection bifurcates between (i) a self-limiting stage for mildly-to-moderately symptomatic patients when the unbiased survival strategy of COVID-19 is disadvantageous against the host immunity, and (ii) a self-amplifying stage for severely-to-critically ill patients when the unbiased survival strategy of COVID-19 is advantageous over the host immunity.
Viral entry: COVID-19 directly enhances its affinity with the functional host-cell receptor angiotensin-converting enzyme 2 (ACE2) and thus targets only stem-like cell types whose ACE2-dependent baseline activities regulate a myriad of homeostatic cellular processes that maintain genome, proteome, ion, energy, and immune system stability in a tissue-specific fashion.
Viral replication and egress: COVID-19 indirectly enhances the activation of the distal promoters of the ACE2 gene in the host cells, resulting in (i) the suppression of ACE2 expression in the host cells, (ii) the hijack of the intracellular machineries of the host cells to enable viral replication and egress, and (iii) the disruption of the homeostatic functions of the host cells.
Viral microenvironment: COVID-19 leverages the disrupted homeostatic functions of the host cells to create a favorable microenvironment that (i) activates the innate immune response to further reduce ACE2 expression to boost viral replication and egress, and (ii) suppresses the adaptive immune response to further reduce host cell death to sustain viral replication and egress.
Viral adaptive mutation: COVID-19 leverages the favorable microenvironment to further enhance its inherently strong adaptive mutability as an RNA virus, thus developing robust resistance to effective but non-curative treatments that predominantly inhibit either viral replication or viral spread and making it unlikely to develop effective vaccines.
Viral latent Infection: COVID-19 can flexibly switch to the latent infection mode under the pressure of strong host immunity and/or during effective but non-curative treatments. COVID-19 can also switch back to the productive infection mode when the host immunity is weakened and/or the effective but non-curative treatments are ended, resulting in inevitable rebound and frequent reinfection among asymptomatic COVID-19 carriers.
Viral latent adversity: When effective but non-curative treatments switch COVID-19 to the asymptomatic latent infection mode, COVID-19 can still chronically disrupt systemic genome, proteome, ion, energy, and immune system homeostases by affecting the baseline activities of ACE2-expressing host cells in multiple organs over years. When the cumulative disruption of multi-level homeostases is sufficient to switch COVID-19 back to the symptomatic productive infection mode, COVID-19 can initiate an accelerate disease progression and trigger severe cytokine storms and fatal comorbidities.
Therefore, COVID-19 is an unprecedented coronavirus that causes both acute respiratory illnesses for symptomatic patients and chronic systemic disorders for asymptomatic carriers.
Effective but non-curative treatments or vaccines may induce a latent preservation of COVID-19 in patients instead of a complete eradication, and the adversity of latent COVID-19 will inevitably trigger a viral rebound, an accelerated progression, and an increased mortality rate.
In light of the foregoing complete aetiology of COVID-19, we hereby recommend the following optimal control & treatment strategy for COVID-19:
- Quarantine but no treatment for asymptomatic carriers and mildly symptomatic patients to leverage the host immunity’s advantage over COVID-19 at the self-limiting stage, resulting in COVID-19 eradication.
- Unbiased curative treatment (e.g. PI3K inhibitors) for moderately-to-severely symptomatic patients to eliminate COVID-19’s advantage over the host immunity at the self-amplifying stage, resulting in COVID-19 eradication.
- Unbiased specialized treatment (e.g. irinotecan + etoposide) for critically ill patients to reduce mortality.
In pandemic settings, public interest in treatment availability and commercial interest in marketing exclusivity are usually misaligned, but we have no doubt that public interest must be prioritized because lives matter above all else.
We have thus chosen to announce those discoveries to the public first without any delay in either applying for patent protection in secret or working with biopharmaceutical companies in private, so as to waive commercial interests once for all to speed up cross-border concerted efforts to solve the unprecedented global crisis posed by COVID-19.
About Demiurge Technologies AG
Demiurge Technologies is a research-based AI-biopharmaceutical company that transforms publicly available life science data into precise disease models in areas with unmet medical needs. The company pioneers a self-correcting scientific approach that validates disease models with the accuracy of AI-based predictions of phase 3 clinical trial outcomes. The company also pioneers a self-sustaining business that commercializes disease models by accelerating the AI-based discovery and development of innovative medicines. Demiurge started in 2016 with headquarters in Switzerland.
AI has been an emerging powerful approach to deeper disease understanding and faster drug discovery, yet it must be put to the most rigorous test to prove its worth under public scrutiny. Demiurge has predicted the outcomes of more than 90 phase 3 clinical trials across multiple therapeutic areas and achieved more than 80% accuracy. Furthermore, we have been inviting the public to witness our future predictions of clinical trial outcomes on Twitter (@DemiurgeTech).
Therefore, we officially put forward AI-based discoveries of the complete aetiology of COVID-19 and the candidate treatments for COVID-19 as scientific hypotheses only and invite the world to validate their potential to solve the unprecedented global crisis posed by COVID-19.
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