by Stacy M. Brown
The coronavirus pandemic has ravaged most of the world, but no one has felt the wrath more than African Americans and communities of color.
Now, it might just be an African American woman who has discovered a desperately needed and life-saving drug to defeat the virus.
Darnisha Harrison, founder, and CEO of Ennaid Therapeutics in Georgia, said scientists working for her company had found a drug that is showing promise in laboratories at blocking the continued spread of COVID-19, the respiratory disease caused by the novel coronavirus.
Based in Atlanta, her company uses its artificial intelligence, or AI, drug-discovery platforms to develop antiviral drugs.
Harrison, a Louisiana State University graduate, said the drug is called ENU200, a repurposed, patent-pending, orally deliverable antiviral drug that was previously approved by the U.S. Food and Drug Administration (FDA) for a different indication.
“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.”
She said the drug shows significant scientific evidence of blocking two proteins that cause COVID-19 from invading healthy host cells and replicating.
In a statement posted on her company’s website on April 27, 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 key CoV enzyme is Mpro.
The results suggest the use of ENU200 as a current, viable treatment for COVID-19 and other CoV infections, Harrison said.
“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,” she said. “The in silico predictions hint that ENU200 match the receptor-binding domain (RDB) by simultaneously blocking the key residues for binding to ACE2, e.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.
“The S glycoprotein of the coronavirus is a class I viral fusion protein located on the outer envelope of the virion that plays a critical role in viral infection by recognizing host cell receptors and mediating fusion of the viral and cellular membranes,” Harrison said.
Additionally, ENU200 blocks CoV main protease, and Mpro is not only a key enzyme for CoV replication but is also responsible for transforming the polypeptide into functional proteins.
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,” she said. “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.
“Such simultaneous blockage may consequently result in enhanced antiviral action to successfully and broadly treat COVID-19 and other CoVs by oral administration,” Harrison said.
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,” she said. “Both viruses are RNA viruses. We think it is noteworthy to mention as proof that ENU200 is indeed an antiviral.”
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.
“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.”