Dewald Schoeman, a doctoral researcher at the University of the Western Cape, South Africa.Credit: Morgan Morris
The wiggly ‘tail’ at the end of the coronavirus envelope protein could help explain why some coronavirus diseases are more virulent than others, a young African researcher has found.
Once considered a minor component among the four structural proteins that give coronaviruses their distinct structure and structural integrity, the envelope protein – or E protein – clocks in at a comparative handful of kilodaltons, a measure of its molecular mass. But the protein may punch well above its weight.
The envelope protein takes its name from its role, as a membrane protein, in the formation of the ‘envelope’ that encases the virus and its genetic material. It is also crucial in pathogenesis, the development of the disease, having been linked to the high levels of inflammation seen in severe cases of COVID-19.
Dewald Schoeman, a doctoral researcher at the University of the Western Cape, South Africa, found that variations in the tail end of the envelope protein may explain why some human coronaviruses – namely those responsible for the diseases, SARS-CoV-1, MERS-CoV, and, SARS-CoV-2, are more virulent than others.
Schoeman’s study compared the envelope proteins of SARS-CoV-1, MERS-CoV, and SARS-CoV-2 with those of 229E and NL63, two less-virulent human coronaviruses commonly associated with the common cold and other mild symptoms. The answer may lie in the conformation or shape of what’s known as the PDZ-binding motif, or PBM, which sits at the tail-end of the envelope protein. This PBM acts like a unique key to a very specific lock (known as the PDZ domain) found on some host cell proteins. The shape of this ‘key’ allows the viral protein to better interact with the host protein, making the virus more virulent.
For his study, Schoeman focused on the PALS1 host protein. In the case of the SARS-CoV-1, MERS-CoV, and SARS-CoV-2 viruses, the PBM boasts an extended coil that is more flexible. By comparison, the PBM of the 229E and NL63 coronaviruses were found to be more rigid.
“We hypothesise that there is a direct link between the increased flexibility of the PBM in the more severe human coronaviruses as it seems to facilitate more stable binding to the PALS1 host protein,” says Schoeman.
While it’s still early days, Schoeman is conducting molecular dynamics simulations that can provide more details about the interaction between the virus’ envelope protein and host proteins. This exercise will perhaps also provide clues on how to short-circuit these interactions.
“Our ultimate aim is to identify a peptide – or other drug – that can bind to all the envelope proteins of the more virulent human coronaviruses,” explains Schoeman’s supervisor, Burtram Fielding, who has studied coronaviruses since 2003 when he was based in Singapore during the SARS outbreak in parts of Asia.
