February 8-14 2021
Which mutations may affect treatments using antibodies?
Amongst the treatments used against COVID-19 are those using therapeutic antibodies. Similar methods used against other viruses have proved ineffective due to mutations in the regions targeted by the antibodies. These mutations may have been caused by selective pressure in a patient during treatment or in an individual infected by a variant which has emerged and which confers resistance to the treatment. In the fight against SARS-CoV-2 it is therefore essential to monitor the appearance of resistant mutations that may render therapeutic antibodies ineffective. Scientists are attempting to anticipate probable mutations using models, and to envisage their possible consequences.
Researchers in Seattle, USA, have, for this reason, developed a method to detect all mutations in the RBD (Receptor Binding Domain) region that affect the recognition of this site by antibodies. The RBD domain, situated on the spike (S) surface viral protein, is the main target of antibodies since this is the domain where binding with the ACE2 cellular receptor occurs, allowing the virus to enter the cell. As regards mutations of a single amino acid, only the mutation of glutamic acid 406 into tryptophan would make the virus resistant to the main therapeutic antibodies. Amongst the variants currently circulating, there already exist mutations that give the virus some measure of resistance against these antibodies. This is the case, for example, with the K417N mutation, present in the South African variant. On the other hand, the N501Y mutation, common to the UK, Brazilian and South African variants, does not bring about resistance.
SARS-CoV-2 E406W mutant:
Mutations in the RBD risk making the virus more resistant. However, these mutations are constrained by the necessity to maintain maximum affinity with the ACE2 cellular receptor so that the virus can enter the cell efficiently.