Impact BioMedical announces that two compound candidates—Linebacker and Equivir—may show promise in the fight against SARS-CoV-2. The compounds, which were identified through molecular docking studies utilizing advanced computational models, will now undergo testing to confirm the prediction.
The news comes from Singapore eDevelopment, the parent company of its U.S. biomedical subsidiary Impact BioMedical, through its scientific research partner GRDG Sciences.
The computer modeling indicated that Linebacker and Equivir compounds successfully inhibit infection by SARS-CoV-2, the virus responsible for the COVID-19 outbreak. The results suggest that the two compounds block 3 mechanisms that are important for SARS-CoV-2 replication and infection: the viral spike interaction point, helicase, and protease.
Recent studies and analyses indicate that Angiotensin converting enzyme 2 (“ACE2”) could be the host receptor for the SARS-CoV-2, notes David Ostrov, PhD, a structural biologist / immunologist in the Department of Pathology, Immunology and Laboratory Medicine at the University of Florida. In previous work, Ostrov had discovered compounds that bind to ACE2, blocking interactions with SARS.
Equivir and Linebacker are undergoing accelerated testing against the SARS-CoV-2 virus. Based on previous work against other coronaviruses such as SARS and MERS, the company is hopeful that it will confirm their preliminary results. “These new compounds with the potential to bind ACE2 and block coronavirus entry into cells were identified by simulation of structural interactions. New drug candidates will be evaluated for effects on coronavirus with GRDG” notes Ostrov.
Identifying ACE2 as the host receptor for SARS-CoV-2 is significant, however, inhibiting ACE2 is problematic as ACE2 is required to regulate cardiovascular system. Therefore, the intention is to modulate ACE2 through a conformational change to prevent interaction with the virus while simultaneously inhibiting the helicase and protease sites of the ACE2 which are necessary for viral replication.
“The coronavirus presents a unique challenge in that it appears to exploit a ‘hand shake’ docking site to human cellular membranes that is atypical of Influenza and Rhinovirus” notes Daryl Thompson, GRDG’s Director of Scientific Initiatives. Influenza, he adds, attaches to human membranes through the use of ICAM or intercellular adhesion molecules to download its genetic material.
It’s now becoming clear, explains Thompson, that the present strain of coronavirus is hijacking the ACE2 or Angiotensin Converting Enzyme pathway to accomplish the same goal. The issue is that ACE2 is essential for maintaining the health of the pulmonary system and may not be a straightforward target for inhibition. Instead, he notes, “we are utilizing both Linebacker and Equivir therapeutics as molecular probes to identify methods to make the ACE2 resistant and less accessible to coronavirus infection.”
“We are constantly pushing to stay ahead of this virus and look to provide meaningful solutions to the current pandemic situation at the soonest,” said Chan Heng Fai, executive chairman and executive director of Singapore eDevelopment.
This research is part of a program conducted by GRDG to adhere to the principles and initiatives established by Project Bioshield and the Biomedical Advanced Research and Development Authority (BARDA) directives from the U.S. Department of Health and Human Services (HHS).