Recently, Prof. Dong-Qing WEI from the School of Life Sciences and Biotechnology (SLSB), Shanghai Jiao Tong University, published a paper in Wiley publisher journal Journal of Cellular Physiology (https://doi.org/10.1002/jcp.30367) in collaboration with Pakistani researchers, titled Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data. This paper used data from UK, South Africa and Brazil to understand the molecular mechanism behind higher infectivity and transmission of the new variants of SARS-CoV-2. This information will help in implementing effective border measures against this virus. The Pakistani newspaper The News has also featured the research achievements on Apr. 7, 2021.

With the emergence of new variants of SARS-CoV-2, the situation around the world is further aggravated. The enhanced transmission of the newly characterized strains may also evade the host immune more robustly. China, Pakistan and other countries are currently facing a new challenge of COVID-19 pandemic and reports of higher number of infections and the circulation of the new variants around the world has created alarming situation. As a result, there is a pressing need to produce and analyze large-scale DNA data of the COVID-19-causing coronavirus, which would help to map a strategy and prevent further spread of coronavirus. Geographic and epidemiological data may further explore routes for defining defending strategies.

Using multiple computational algorithms, the team led by Prof. Dong-Qing WEI disclosed that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The study also explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. The research revealed that the RBD domain of the Spike glycoprotein is continuously subjected to positive selection pressure and further potential variants may pose more serious threat to the public health and safety.

In addition, the study also reported that the stronger binding of the newly emerged variants is mainly due to the electrostatic contribution and these findings further suggest that the key differences in the interaction pattern are noteworthy for higher infectivity. The study also revealed the structural-dynamics features associated with these new variants and their binding affinity using real time free energy calculation methods. This scientific work could also assist in designing small-molecule inhibitors that can specifically abrogate the ACE2-spike complex association, which may help to reduce disease burden and assist recovery of patients.

Computational structural biology tools, like alphafold2, are re-shaping the biological research, which can substantially assist the fight against SARS-CoV-2.  The process of finding a magic molecule (drug) to defeat the severe health challenge can be accelerated by the recent artificial intelligence technology. Further studies are required to monitor the multiple co-circulating SARS-CoV-2 strains and its spread around the world.