A study developed at the IGC, in collaboration with ITQB-NOVA and NOVA Medical School, has discovered a structural part of the Spike protein that is prone to evolving into new Covid-19 variants.
Research by the Instituto Gulbenkian da Ciência (IGC), in Oeiras, has discovered two structural points of one of the proteins of the virus that causes COVID-19, which are prone to evolving into new variants. These two structural points of the Spike protein escape the immune response, going more unnoticed by antibodies generated after vaccination or infection.
The study, published in the journal PLOS Pathogens, was led by Maria João Amorim, principal investigator of the IGC, and focused essentially on the structure of the Spike protein of SARS-CoV-2. The research involved teams from ITQB-NOVA and Centre for Chronic Disease Studies of NOVA Medical School, led by Cláudio M. Soares and Helena Soares, respectively.
To determine the effect of changes in the Spike protein, the research team used techniques that allow it to be expressed in non-harmful viral particles that are easy to study and do not require high-security laboratories. By adding antibodies produced after infection or vaccination to cells and viral particles in culture, it was possible to measure the protection that these antibodies exerted against each variant.
“Using this technique, we detected two mutations at different points in the Spike that cause the virus to evade antibodies generated after infection or vaccine administration. We know that the virus is changing and it is important to be able to understand and predict which mutations affect the course of the infection”, explained Maria João Amorim, stressing that “this type of knowledge is crucial for us to be able to anticipate the virus and adjust our strategies to combat the pandemic”.
One of the mutations noted, called 484, was already known and is included among the variants of concern from Brazil, South Africa and India. The other mutation, 494, appears as a new structural point that could be altered in the SARS-CoV-2 virus.
“The 494 mutation is on the list of variants currently under investigation by the Centers for Disease Control and Prevention and Public Health England. With this study we were able to prove that it allows the virus to escape the antibodies. This proves that we should investigate the need to develop vaccines and therapies that could respond to these mutations, as well as determine the mechanisms that allow the virus to replicate without being unrecognised,” added the project’s principal investigator.
Through molecular simulation and the analysis of dozens of structures, it was possible to predict which mutations could give the virus an advantage, allowing it to escape antibodies, without losing the ability to infect efficiently. “When we looked at this data, there were two points that stood out as having the potential to harbour mutations that could be dangerous”, recalled researcher Diana Lousa, from ITQB-NOVA.
Next, the mutations were tested experimentally, where the potential to escape antibodies was proven, something that “would not have been possible without close collaboration between experimental and computational work”, according to researcher and Director of ITQB-NOVA, Claúdio Soares.
By mid-April 2021, there were more than 140 million cases of COVID-19 worldwide. The high transmission rate of the virus inevitably increases the probability of the evolution of new variants. Among these variants, there are those that give the SARS-CoV-2 virus the ability to evade the immune system, escaping the host without compromising its replication.
