Black-owned laboratory uses artificial intelligence-based drug discovery platform to develop treatment for COVID-19
By Stacy M. Brown
NNPA Newswire Senior Correspondent
The novel coronavirus has ravaged most of the globe, but in the U.S., African Americans and other communities of color have disproportionately born the lethal impact of the pandemic.
Darnisha Harrison, a Louisiana State University grad and founder and CEO of Georgia-based Ennaid Therapeutics, says that scientists working for her company are developing a drug-based therapy whose laboratory tests continue to show promise. If successful, her scientists’ solution could be instrumental in blocking the continued spread of COVID-19.
Ennaid Therapeutics uses artificial intelligence (AI)-based drug discovery platforms to develop antiviral drugs.
The drug that shows so much promise has been labeled ENU200, a repurposed, patent-pending, and orally deliverable antiviral drug that was previously approved by the U.S. Food and Drug Administration (FDA) for a different indication. The development of ENU200, as a therapeutic, is targeted to treat the up to 80 percent of asymptomatic, mild to moderate cases of COVID-19 viral infections.
“Our science strongly suggests that ENU200, a repurposed drug with a well-established clinical and safety profile, has the potential to be a broad solution to address the COVID-19 pandemic and, specifically, the near 80 percent of coronavirus cases that are asymptomatic, mild to moderate,” said Harrison. “Key to ENU200 is its target of two proteins on the SARS-CoV-2 virus that interfere with the virus’ ability to enter healthy cells and its replication. Additionally, unlike other COVID-19 drugs in development, which must be administered via injection or intravenously under the care of a physician, ENU200 can be administered orally, thus enabling in-home treatment for COVID-19 infections.”
“The FDA has been very supportive at fast-tracking review every step of the way, and that is true around the world,” Harrison told WBRZ-TV in Baton Rouge
“We anticipate the clinical trials could start within 90 days. The clinical trial itself could take a month. We feel quite optimistic that in the 120-day window, when our clinical material would be ready, we could have a drug that could be safe and effective at treating COVID-19.”
In a statement posted on the company’s website in April, Harrison noted that the rationale for developing ENU200 arose from a bioinformatic search for in-silico identification of prior-approved chemical compounds blocking the CoV proteins, spike S glycoprotein and Mpro. A Mpro is a key CoV enzyme.
The results suggest the use of ENU200 as a current, viable treatment for COVID-19 and other CoV infections, Harrison stated. “ENU200 blocks the S glycoprotein of CoV, which is responsible for host cell attachment and mediating host cell membrane and viral membrane fusion during infection.”
“The in-silico predictions hint that ENU200 matches the receptor-binding domain (RDB) by simultaneously blocking the key residues for binding to ACE2, .g., Gln493 and Asn501. This function is key to the viral life cycle and a major target for antiviral drugs, such as ENU200 and vaccines,” said Harrison.
All available data demonstrate that Mpros are largely conserved structures, Harrison added. “The combination of such unique features reveals that ENU200 blocks COVID-19 and other coronavirus action by specifically targeting the Mpro active site. Before showing specific blocking/antiviral activity against S glycoprotein and Mpro of COVID-19, ENU200 had previously shown protease inhibition of a different virus, indicating that ENU200 interacts with two targets.”
The in-silico drug discovery platform applied state-of-the-art codes by combining virus targets and a wide range of libraries of compounds, Harrison added.
Computational steps include:
• A first geometrical and electronic optimization of the drug-candidates based on quantum chemistry within density functional theory (DFT) methods.
• The resulting refined structures were next implemented in blind docking calculations, an approach that allows to scan the whole protein surface in the search of main binding pockets.
• Only the best poses are retained for the analysis, so that the provided structures correspond to the drug-target interaction with the largest affinity.
Harrison said in vitro work is now being completed.
“Currently, we have in vitro and in vivo data supporting ENU200’s inhibition of a viral protease in a different viral infection. Both viruses are RNA viruses. We think it is noteworthy to mention as proof that ENU200 is indeed an antiviral,” she said.
Since ENU200 has a well-tolerated safety profile, Ennaid is confident that being allowed to treat the up to 80 percent asymptomatic, mild/moderate cases of COVID-19 infections will reduce COVID-19 viral shedding and severity, Harrison noted.
Ennaid believes it can quickly bring ENU200 to market by treating patients with COVID-19 in a Phase 3 in-home, self-dosing clinical trial of patients with asymptomatic, mild to moderate coronavirus infections utilizing their iClickCare® secure clinical reporting software service to monitor the in-home trials.
“ENU200 would also reduce worldwide fear and allow continued economic and operational development worldwide,” she said. “ENU200 can mitigate COVID-19 and may even cure coronavirus.”