M-LIFE™, a biotech and life sciences company, has identified six marketed drugs suitable for repurposing as possible therapies for COVID-19.
NASHVILLE, TENNESSEE – M-LIFE™, a biotech and life sciences company, has identified six marketed drugs suitable for repurposing as possible therapies for COVID-19. These drugs have not been previously indicated via the mainstream media. Additionally, these newly identified prospects directly target the COVID-19 virus as opposed to the illness progression (e.g., cytokine storm). The M-Life™ list of prospective repurposed drugs for the treatment of COVID-19 includes: tirofiban cardiovascular, ketoconazole - antifungal, lacidipine - hypertension, pilsicainide - antiarrhythmic, suramin - sleeping sickness, and uradipil - hypertension.
According to M-Life™ Chief Discovery Officer Dr. Peter Crooks, the identified molecules offer the possibility of new options for treatment. “None of the identified drugs are on anyone’s radar for repurposing to treat COVID-19,” he said. “The big benefit of using repurposed drugs is that the safety, side effects and dosing are already known through experience garnered from FDA approval for their original intended use. Pending some additional testing, it’s quite possible that all of the identified repurposed drugs could be used as treatments within months rather than a decade or more required for an entirely new molecule to go through the testing, clinical trial phases, and FDA approval process.”
Dr. Crooks continued, “Although there are many therapeutic strategies for the treatment of COVID19, our efforts focused on the identification of existing drugs that directly affect COVID-19 virus infection and disease progression. On the most elemental level, COVID-19 disease progression is dependent upon the rapid replication of the virus. In viral replication, as with COVID-19, the virus hijacks human genetic material and repurposes the nucleic acids for its own replication. By interfering with the COVID-19 nucleic acid enzymes, including helicase, protease, and polymerase, the virus cannot create viral copies efficiently. This translates into lower post-infection viral loads and slower disease progression.”
The M-Life™ technical evaluation assessed the ability of a cross-section of current on-market drugs to inhibit viral enzymes using several M-Life™ proprietary algorithms. “The M-Life™ algorithms uniquely identified key chemical features within a ‘molecular systems’ construct,” said M-Life™ President & CEO Ted Moskal. “To help ensure validity, drugs currently being used to treat COVID-19 were also tested and the results aligned with current outcomes,” he added.
M-Life™ Chief Scientist Dr. Jon Wilkes gave an overview of the process used to derive the list of repurposed drugs. “M-Life™ evaluated 2426 molecules, on market drugs and experimental chemicals (used to qualify algorithm predictions). The repurposing process involved codifying the compounds, and screening against viral enzyme targets using several different models all approaching the analysis from different perspectives. Also, each of the 2400 molecules were evaluated via M-Life’s™ four different enzyme inhibition algorithms—polymerase, protease, helicase, and neuraminidase. Arguably, neuraminidase is not a relevant target for COVID-19, however, this in part served to cross-validate the results for specificity and sensitivity. Several drugs currently used for the treatment of COVID-19 served as benchmarks to evaluate actual versus predicted algorithm performance. Drugs with no intramuscular (IM) or oral route of administration were removed from the list and the best performers via our algorithms were ranked to produce the Top Six list.”
“We are confident in the algorithm predictions for a variety of reasons.” These include:
- Algorithm predictions aligned with current drugs being used to treat COVID-19, both those that seem to have some efficacy and those that do not.
- The form of the results was both consistent with therapeutic on-market experience as well as the technical attributes for good predictive models.
“Our algorithms are built upon the principle of triangulation-many models that approach efficacy from different perspectives. When all of the models point to the same result, it builds confidence in the validity of the models. Our results indicated that the molecular attributes associated with efficacy with regard to COVID-19 treatment are rare, unique to one specific enzyme (i.e. polymerase, protease or helicase) and that these attributes are not unique to one drug class. It’s our belief that the most important factor is the alignment between actual and predicted results.
Model predictions for drugs presently being used to treat COVID-19 aligned with the current clinical experience using them, serving as benchmarks. For example, computational predictions for Ifenprodil® (Algernon) and Atazanavir® (Gilead) aligned with current clinical efficacy experience toward the treatment of COVID-19. Our algorithms flagged hydroxychloroquine as a poor performer also aligning with clinical experience. As a point of curiosity, we generated predictions for several additional drugs touted for possible treatment of COVID-19 and none of them were among the top candidates proposed for repurposing. The final six drugs were highly selective toward one specific enzyme (polymerase, helicase or protease) but not all. The highest-ranking candidates that were computationally identified by M-Life™ algorithms in alphabetical order are: ketoconazole, lacidipine, pilsicainide, suramin, tirofiban, and uradipil.”
When asked about some specifics regarding the M-Life™ proprietary computational methods, Dr. Wilkes said, “Each of the COVID-19 specific algorithms fall under two Company platform technologies:
- P2L™ (pattern-to-lead class of proprietary platform)- The descriptors employed by P2L™, the computational methods themselves, and associated proprietary software for interpreting the sub-structural components’ contribution to activity – serve together to enable P2L™ function. Collectively, they reveal the mathematical and chemical underpinnings for predictions of molecules with unknown activity. They also permit the directed design of completely new molecules.
- MiST™ proprietary platform (Molecular in Silico Tomography)- In the MiST™ computational suite, the ‘object’ is a molecule and the ‘cross-section’ is derived from a selected subset of its atoms, their electronic states, and their intramolecular attributes; which are derived from a P2L™ models. These cross-sections constitute the collection of molecule features reliably associated with that model’s therapeutic and toxicological properties. MiST™ enables the composited build-up of cross-sections to form a holistic view of molecular systems toward a particular therapeutic endpoint. Most importantly, the MiST™ suite provides molecular rankings for molecules, whether the target is, for example, reducing blood pressure or treating a viral infection.
In short, P2L™ allows us to derive ‘how’ individual molecular features work in relation to a specific endpoint and MiST™ facilitates the comprehensive analysis of ‘what’ all the individual features will do in a composited form, thus identifying the ‘best’ molecules.”
The Company has further research underway relative to possible off-target effects, both toxicity and side effects, for repurposed drugs and plans on sharing additional information in the near future. According to Moskal, M-Life™ plans on releasing its data and internal assessment to the public in the upcoming weeks. “It’s simply the right thing to do,” Moskal said. “The COVID-19 pandemic is unprecedented, and these troubling times are opportunities for small companies like ours to step up. We hope our findings will stimulate additional research on the six drugs our Team identified. It’s our belief that additional therapeutic options will greatly improve the chances of identifying one or more highly effective treatments for COVID-19.”
About M-Life™
M-Life™ is a life sciences drug discovery company, which is focusing on the development of new drugs, agricultural and diagnostics related chemicals. Whether a new antibiotic, non-opiate analgesic or environmentally friendly herbicide, the Company aims to address gaps in the present life sciences markets making life better. To learn more about M-Life™, visit www.mlifesciences.com.
M-Life™ Cautionary and Disclosure Statement
This press release contains statements relative to predicted performance using proprietary algorithms. The actual performance of these drugs in treating COVID-19 cannot be fully assessed until their usefulness has been determined via treatment of the illness. Some care must be taken relative to assertion of a drug’s projected therapeutic efficacy. The M-Life™ predictions were specific to protease, helicase and polymerase. It’s possible that some of the drugs not identified here could operate efficaciously via another modality. The Company does not have any current or pending relationships associated with the identified prospective repurposed drugs for the treatment of COVID-19. A copy of the M-Life™ internal technical study will be made available in the upcoming weeks. Additionally, the Company plans on sharing additional information relative to possible offtarget effects associated with the list of repurposed drugs in the near future.
