1. University of Virginia - https://med.virginia.edu/cell-biology/recent-publication/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection/

Reference for Mode of Action

Apilimod acts as an entry inhibitor, a mechanism proven by its success in blocking Ebola virus infections. As a phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) inhibitor, it prevents alternative splicing triggered by the PIKfyve protein kinase. This action blocks the entry of infectious substances into the cytoplasm, making it a promising candidate for treating filoviral infections.

University of California, Santa Cruz

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Apilimod, also known as LAM-002A is an anti-cancer drug that is viewed to have high potential in effectively treating COVID-19.

In fact, Dr. Sumit Chanda, a lead investigator at the Sanford Burnham Prebys Medical Discovery Institute claims that apilimod is one of the top candidates to represent a treatment option for COVID-19. 


Apilimod as a Treatment for COVID-19

Apilimod’s properties come from its primary mechanism of action, which is its disruption of lysosomal function.

By inhibiting the lipid kinase PIKfyve, apilimod induces cell apoptosis and is, consequently, able to prevent the autophagy of foreign and infectious substances. In addition, PIKfyve inhibition results in the increase of endolysosomal organelles. Since PIKfyve is also a primary regulator of endosome activity, apilimod’s efficiency is further increased as endosomes are how many viruses actually deliver their genetic material into a host cell and are often the beginning of a viral infection.


Mechanism of Action

Yale University’s School of Medicine and AI Therapeutics, a biopharmaceutical company, launched a multi-institutional clinical trial to test the safety and efficacy of using apilimod to reduce virus levels in infected individuals. While Yale conducted the study, AI Therapeutics, founded by a Yale alumnus, owned the intellectual property rights to the drug. The study was expected to enroll 142 newly diagnosed patients. Murat Gunel, a Yale professor and an advisor at AI Therapeutics, stated that LAM-002A (apilimod) held promise as a powerful therapy for COVID-19 patients to prevent disease progression, hopefully avoiding the need for hospitalization. Gunel and other researchers involved in the study were hopeful that apilimod would be able to prevent the development of COVID-19 after exposure, particularly among high-risk populations, such as the elderly community.

Yale University and AI Therapeutics Clinical Trial of Apilimod for COVID-19 (2021 Completion)

Dr. Ricardo Battaglino from the University of Minnesota claims that apilimod is five times more effective in treating cell cultures with COVID-19 compared to remdesivir [1]. Battaglino coordinated with a team in Chicago to develop their own version of apilimod that would be 99% pure and geared toward treating COVID-19 [1]. Researchers working with cells in culture found that the amount of their "apilimod-like" drug needed to successfully block the virus is one-fifth to one-tenth of what is currently needed when using remdesivir [1]. The results of the study suggest that the drug may help treat patients with severe cases, while also being able to prevent the progression from mild to severe symptoms [1]. Furthermore, with the inevitability of more coronavirus outbreaks in the future, Battaglino believes that apilimod "is going to be effective against any coronavirus because the way it works is not specific to virus strain" [1].

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