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LATEST UPDATES » Special Issue 1, March 2020 – Coronavirus Outbreak       » Vol 24, No. 03, March 2020 – Modern-Day Nostradamus: Predicting the Peak of COVID-19 in China with Mathematical Modelling       » A remote-controlled smart platform for organ repair       » COVID-19 and its genetic relationship with other coronaviruses       » Shedding Light on COVID-19 Vaccine Development       » AI enables whole-slide imaging for diagnosis of nasal polyps       » East meets West: cancer therapy using acupuncture and electrochemistry      
Vol 24, No. 03, March 2020For e-subscribers (PDF)
EYE ON CHINA
COVID-19 and its genetic relationship with other coronaviruses
A study has revealed that COVID-19 has an infection mechanism same as that of SARS, despite their considerable differences in genetic sequence.

"To understand the origin of [COVID-19] and its genetic relationship with other coronaviruses, we performed phylogenetic analysis on the collection of coronavirus sequences from various sources," said Professor Pei Hao at Institut Pasteur of Shanghai, lead author of the paper published in Science China Life Sciences.

The results showed that COVID-19 belongs to the Betacoronavirus genera, which are enveloped, single-stranded RNA viruses that infect wild animals, herds and humans, resulting in occasional outbreaks and more often infections without apparent symptoms.

COVID-19 shares with SARS a common ancestor that resembles the bat coronavirus HKU9-1, and the authors suggested that bats being the native host of COVID-19 would be a logical deduction, though it remains likely there was intermediate host(s) in the transmission cascade from bats to humans.

However, when they compared the genome sequences, they found that there is considerable genetic distance between COVID-19 and SARS, and even greater distance to MERS. There was especially high sequence diversity in the ORF1a and spike (S-protein) genes between COVID-19 and SARS.

This observation raised an important question as to whether COVID-19 adopted the same infection mechanism as SARS, which exploited its S-protein’s high affinity to human ACE2 receptor for invasion into cells. “We performed structural modelling of [COVID-19’s] spike protein that is critical for coronavirus-host interaction, and evaluate its ability to mediate human infection," said Prof. Hao.

Their computations revealed that the binding free energy for COVID-19’s S-protein to ACE2 is –50.6 kcal/mol, which is considered significant binding affinity (despite being a little weaker than that between SARS S-protein and ACE2 which is –78.kcal/mol). This was apparently to the authors’ surprise as four out of five important interface amino acid residues were different in the two S-proteins.

They then realized that the differences did not alter the structural conformation; the 3D structure in the binding domain was almost identical, thus maintaining similar van der Waals and electrostatic interactions.

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