The present COVID-19 disease caused by Severe Acute Respiratory Syndrome (SARS) coronavirus-2 with its epicenter, reported from Wuhan, China during December 2019, has rapidly become a pandemic resulting in an alarming number of infections and deaths worldwide. It is known that bats are natural reservoirs of SARS coronaviruses. The SARS coronavirus constantly gets mutated in bats and jumps across species, thereby animals such as civets and pangolins acquire the virus. Further mutations of the virus and human contact with these host animals would result in human infection leading to the severe respiratory disease.
A SARS coronavirus protein named – Spike, that forms a crown-like appearance “Corona” specifically binds to human angiotensin converting enzyme-2 (ACE-2) receptor. A crucial question addressed is, what changes might have occurred in SARS coronavirus genomes and the spike proteins during evolution that made the virus capable of causing human infection? Prof. Lalitha Guruprasad at School of Chemistry, University of Hyderabad analyzed complete genomes and spike protein sequences of several SARS coronaviruses from bat, civet, human and human SARS coronavirus-2. Her study revealed that “three sequence regions and a disulfide bridge are present only in SARS coronavirus spike proteins that bind ACE-2 receptor, whereas, these sequences are absent in bat SARS coronaviruses that are incapable of causing human infection”. Mutations of a more transmissible form of SARS coronavirus-2 subsequently reported by the Los Alamos National Laboratory, USA is associated with one of the sequence regions identified by the University of Hyderabad, India. The sequence motifs that are specific to human SARS coronavirus-2 that interact with ACE-2 can be exploited as potential candidates for antibody design. Her study also cautions that some bat SARS coronavirus genomes are still evolving and may eventually acquire the capabilities to infect humans and pose a potential threat in future.
Figure legend: Illustration of the region of specific contact (green) in SARS coronavirus-2 spike protein (blue) with human ACE-2 receptor (red).
Reference: Guruprasad, Lalitha (2020): Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition. ChemRxiv. Preprint. https://doi.org/10.26434/