Both compounds block integral viral mechanisms for SARS-CoV-2 replication and infection
SGX-listed Singapore eDevelopment Ltd (SeD; SGX:40V) has announced that its wholly-owned U.S. biomedical subsidiary Impact BioMedical, Inc.
has through its scientific research partner GRDG Sciences, LLC. conducted molecular docking studies utilizing advanced computational models, indicating that its Linebacker and Equivir compounds successfully inhibit infection by SARS-CoV-2, the virus responsible for the COVID-19 outbreak.
The results indicate that the two compounds block 3 integral viral mechanisms for SARS-CoV-2 replication and infection: the viral spike interaction point, helicase, and protease.
Equivir and Linebacker are undergoing accelerated testing against the SARS-CoV-2 virus and data is expected to confirm efficacy based on previous work against other coronaviruses such as SARS and MERS. 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).
On 11 March 2020, the World Health Organisation Director-General, Dr.
The World Health Organisation has therefore made the assessment that COVID-19 can be characterised as a pandemic and this is the first pandemic caused by a coronavirus, he added.
"Recent studies and analyses indicate that Angiotensin converting enzyme 2 ("ACE2") could be the host receptor for the novel coronavirus 2019-nCoV/SARS-CoV-2," says Dr. David Ostrov, PhD, a structural biologist / immunologist in the Department of Pathology, Immunology and Laboratory Medicine at the University of Florida, who previously discovered compounds that bind to ACE2, blocking interactions with SARS.
"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."
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 research is headed by Mr. Daryl Thompson, GRDG's Director of Scientific Initiatives.
"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. Influenza attaches to human membranes through the use of ICAM or intercellular adhesion molecules to download its genetic material.
"It's now becoming clear 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, 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," says Mr. Thompson.
"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 Mr. Chan Heng Fai, Executive Chairman and Executive Director of SeD.
GRDG's Chief Scientific Advisor, Dr. Roscoe M. Moore, Jr., the former United States Assistant Surgeon General and the former Epidemic Intelligence Service Officer at Centers for Disease Control and Prevention or CDC, said, "These results are encouraging and signal the potential of Linebacker and Equivir to be important solutions to the coronavirus pandemic."
GRDG is also advised by Lieutenant Colonel William H. Lyerly Jr., retired U.S. Army Medical Service Corps Officer, and retired Career Senior Executive / Scientific Professional at the U.S.
Department of Homeland Security. Lieutenant Colonel Lyerly also served as senior official in the U.S.
Department of Health and Human Services, the U.S. Agency for International Development, and U.S.
Executive Office of the President (White House). Lieutenant Colonel Lyerly states, "the importance of technologies such as Linebacker and Equivir cannot be understated as the global spread of the virus continues to accelerate."