Two existing drugs represent potential new targets for COVID-19

A new lab-based study is based on SARS-CoV-2 (COVID-19) because two existing drugs, including those developed by researchers at Harvard Medical School and Boston Children’s Hospital, infect human cells in dishes. The virus that causes) is inhibited.

Originally developed a few years ago, both drugs, vacuolin-1 and apilimod, target a large enzyme called PIKfyve kinase.

Prior to this study, little was known about the role of this enzyme in COVID-19 infection. Work that needs to be duplicated Human trial, Suggests potential new targets for COVID-19 therapy.

Survey results were published on August 6 PNAS..

“Our findings indicate that targeting this kinase via a small antiviral agent against SARS-CoV-2 is an effective strategy to reduce the progression or severity of COVID-19. It shows the potential.” Pediatrics Professor at Boston Children’s Institute, Boston Children’s Laboratory, HMS.

Kirchhausen discovered vaccine-1 16 years ago. Apilimod was developed by a company called LAM Therapeutics.

After Ebola

When Kirchhausen first discovered vacuumolin-1, he published a paper explaining what it does in various cell types.

A few years later, he started a long collaboration with colleagues at HMS at Center for Excellence in Translational Research focusing on small molecules against emerging viruses.

They showed that vacuumolin-1 and apilimod, which have similar chemistries, are both effective inhibitors of Ebola virus. They did not publish the results at that time.

When COVID-19 began to hit the United States early in March, Kirchhausen’s labs diminished, as did many other labs in the country. However, before turning off the light, he remembered that the kinetics of Ebola virus cell entry was similar to that of coronaviruses like SARS-CoV-2.

Kirchhausen contacted co-author Sean Whelan, who was on the Center for Excellence team at HMS, but then moved to the University of Washington. Duo conducted a cell biology study using the SARS-CoV-2 virus in the Whelan lab.

“Within a week, apilimod was found to be very effective in preventing SARS-CoV-2 infections. Human cell “In the lab,” said Kirchhausen, who first published this discovery on the bioRxiv preprint website in April 2020.

The preprint also included a review of the efficacy of apilimod against Ebola and SARS-CoV-2.

“We, like apilimod, have found that vacuumolin-1 in the laboratory is a very potent inhibitor of viral infections,” Kirchhausen said.

In an unexpected coincidence, an irrelevant group, with 12,000 clinical stage or FDA-approved small molecule screens, found apilimod to be one of the best drugs to inhibit SARS-CoV-2 viral replication. I have posted a paper showing. That paper was published after that Nature..

Currently undergoing clinical trials

Apilimod’s parallel development finally landed at AI Therapeutics after showing no benefits in Phases I and II Clinical trial Its original purpose for the treatment of autoimmune diseases.

Although these trials were unsuccessful, apilimod’s clinical trials of 700 healthy volunteers and patients showed no significant side effects even when given at high doses to patients for over a year. It was

This spring, using some of the data from Kirchhausen’s bioRxiv paper and information from drug screening by others, AI Therapeutics will see if apilimod reduces the severity of COVID-19. Approved by the FDA.

In late July, AI Therapeutics announced a new randomized, double-blind, placebo-controlled trial with apilimod known as LAM-002. It tests the safety, tolerability, and efficacy of apilimod in reducing viral load in approximately 140 patients with early-onset COVID-19.

Kirchhausen plans to administer other drugs in addition to PIKfyve kinase inhibitors in the future.

“Maybe an anti-inflammatory drug or other drug that targets an activating protease Virus “In addition to something like our drug that lowers the load of the virus because of cell invasion,” he said.