14 Apr Coronavirus Camouflage Can Make Some Antibodies Useless
MedicalResearch.com Interview with:
Dr. Naveen Vankadari PhD
Monash University, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The recent outbreak of pneumonia-causing COVID-19 pandemic is an urgent global public health issue. It is critical to understand and unravel the key difference of COVID-19 or SARS-CoV-2 with the previous coronavirus (SARS and MERS) infections. Specifically, structural and molecular dynamics which underline the mechanism of viral infection.
The study first addresses the structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which open the arena in understating the viral attachment to the host cell. The study also provides the first and complete sequence alignment of spike glycol protein from COVID19 and SARA-1, showing novel insertions and deletions that highlights the uniqueness of COVID19 and underlies the differential interaction mode.
The study also unravels how this new coronavirus camouflages in humans through its unique glycosylation of spike glycoprotein, which makes the most of neutralizing antibodies useless. Furthermore, In addition to known ACE2 receptor in human, the study discovers the human CD26 as another potential receptor of COVID-19 for host adhesion and hijacking.
MedicalResearch.com: What should readers take away from your report?
Response: It is critical to understand the molecular and structural interplay between the viral and human proteins, which assist in developing therapeutics. Readers and researchers also need to know that viral spike protein undergoes glycosylation, which shields the virus from different various antibodies.
The structural and molecular dynamics studies of this research present another possible human target for COVID-19, which abet in finding new therapeutics to block the interaction between the virus and human CD26 a key immunoregulatory factor. This observation guides us to suggest that COVID-19 may share combined infection modes with that of SARS-1/MERS and there might be other possible targets which warrant further investigation.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Although viral entry into the host cell is mostly mediated by the receptors, the virus does adopt several pathways to hijack the host defence system for its entry. Drugs or inhibitors targeting receptor binding could only reduce the infection. For example, ACE2 was the first identified receptor COVID-19 and many research groups around the globe just focus to block ACE2 interaction. Later reports show CD26 as another possible receptor and discovered protease such as Furin and TMPRSS2 play a vital role in virulence and cell entry making the ACE2 of minimum importance as the virus can bypass the ACE2 interaction. It is critical to look for the different viral/host proteins and targeting them at the same time.
Combination of drugs targeting different viral proteins could be more promising. While designing or developing the antibodies, the glycosylation pattern of virus spike glycoprotein should be taken into consideration or the antibodies are useless. Unravelling the structural features of viral proteins and their interactions with the different human targets open the arena in rising bonafide antibodies and have great implications in the development of inhibitors or therapeutics.
“When we are getting ready to battle with a dangerous virus like SARS-CoV-2, we need to be prepared with the various types of weapons in our armoury”
This work was supported by Monash University and National Health and Medical Research Council of Australia
Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26
Vankadari, N. & Wilce, J. A.,
Emerging Microbes & Infections.
2020 Mar 17. Published DOI:10.1080/22221751.2020.1739565
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