IIT Madras studies say the spike protein-human cell-binding mechanism holds clues for Covid drugs
According to the report, recognising the interactions of spike protein at the human receiver site ACE2 can help to identify ways to minimise coronaviruses and treatment options.
New Delhi: The cause of the devastating infection and transmission of Covid-19 is due to the high energy and interaction region between the SARS-CoV-2 spike protein, the human ACE2 receptor, considered a point of entry for the coronavirus to hook up on and infect a broad range of human cells, an IIT Madras study found.
The research team performed an analysis of three human-impact viruses — SARS-CoV, which appeared in China in 2002; the NL63, a strain that was first detected by the Netherlands in 2004 as a common cold coronavirus; and the SARS-CoV-2 as a cause of the existing Covid-19 pandemic.
Researchers have found that the spike-protein-ACE2 interaction region in the human body plays a key role in determining the magnitude and transmission potential of coronaviruses.
ACE2 also referred to as the angiotensin-converting enzyme 2, provides an entry point where the coronavirus hooks and infects a broad variety of human cells. Simpler, this protein serves as the gateway to the human body for the coronavirus. ACE2 is found in the linings of various cell types and tissues including the lungs, heart, vessels of the blood, kidneys.
On 16 November 2020, Proteins: Structure, function, bioinformatics published the study entitled “Why ACE2 binding Coronavirus strains SARS- CoV/SARS- CoV 2 wild and NL63 mild.” This Monday, IIT researchers shared their results.
The research team has been led by Prof. M. Michael Gromiha, Biotechnology Department, IIT Madras, Bhupat and Jyoti Mehta, School of Bioscience, IIT Madras, and Dr Puneet Rawat and Dr Sherlyn Jemimah, IIT Madras researcher. The team worked with the University of Madras Prof. P.K. Ponnuswamy, former Vice-Chancellor.
‘SARS-CoV-2 most serious infection’
The scientists wanted to understand why recent coronaviruses epidemics such as SARS-CoV and SARS-CoV-2 were more fatal than the common cold, which cause coronaviruses such as NL63.
To this end, they examined how the spike proteins of various virus strains interact with the human cells’ ACE2 receptors and how this interaction affects their transmission capacity and disease severity.
In determining the severity and transmission potential of coronaviruses it was found that the interaction between spike protein of viruses and ACE2 in the human body around hydrophobicity and energy-interaction. Hydrophobicity is the property of water repulsion.
“We find SARS-CoV-2 by testing its properties to be more serious. We found that this new virus mutation has a high energy interaction… This means that the spike virus protein and ACE2 are very common and have a very close bond,” said Dr Micheal Gromiha, the study’s lead researcher at ThePrint.
“When two bodies are in contact, for instance, high energy of interaction between them will result in broad common areas,” he added. “The seriousness of the disease is high when the binding strength between both surfaces is high.”
In comparison with SARS-CoV and SARS-CoV-2, the team also found that NL63 has special ACE2 binding places.
According to researchers, understanding host-pathogen interactions can help to identify ways to minimise the severity of serious coronaviruses that cause severe disease and to establish successful therapeutic interventions.
“The similarities and differences in the spike-protein of the three viruses listed in this study may help researchers understand the structural behaviour, binding site properties and aetiology of the binding of ACE2, the acceleration of the screening of potential lead molecules and the production or recycling of therapeutic medicines,” claimed the study’s authors.