Both of the new mutant strains on SARS CoV2 found in UK and S. Africa have N501Y mutation. The preprint paper quoted below tells this mutation causes stronger interaction between S1 spike protein of the virus and hACE2 while it decreases that with anti spike protein antibody.
It may mean this mutant strains could prevail more efficiently than the original strain and even could be more toxic since it would hinder the antibody interaction to S1 spike protein, that is, neutralizing antibody reaction. As this author mentions, it might be related with the effect of the vaccines.
The other report analyzed the characteristics of antibody produced in infection. There is a kind of IgG antibody which has a negative effect for self defense. The article says it might be the reason why convalescent phase plasma has not given dramatic effect on seriously ill patients.
There are still problems with this pathogen to overcome the outbreak. The N501Y+strain seems to already prevail in various countries. We should be even more cautious not to get infected until the vaccines prove to be effective for the strain.
Abstract
The N501Y mutation in Covid-19 arise many question but a small amount of data are currently available. An urgent understanding of N501Y mechanism of action at molecular level is highly required. Here, we present the preliminary results of our Free energy perturbation (FEP) and Molecular dynamics (MD) calculations for the interaction of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody, STE90-C11, derived from COVID-19 patients. The results shown that the S1 RBD-ACE2 interaction was increased whereas those with the STE90-C11 antibody significantly decreased (over about 160 times). This may explain the observed in UK more spread of the virus but also emerge an important question about the possible human immune response and already available vaccines. Indeed, the latter may still act well but our data indicate some possible reduction of their effect. Further studies of N501Y mutation are need.
Competing Interest Statement
The authors have declared no competing interest.
It makes a lot of sense but I wonder why Dr Fratev to model STE90-C11, when there are about a dozen antibodies that have been isolated now, for use in convalescent therapies. I don't think he explains how he knows that, but he sure chose the right one. I would like to see him model some of the other antibodies and see some other people challenge this, since this kind of model looks like a magic box to me. If this is right, it's bad news.
ReplyDeleteThis antibody seems most potent one reacting RBD of the viral spike protein. It was also thought to be mutation tolerant so far as known until now. That was the reason why the researcher had chosen to study this VOC strain. Are you Stephen? If you show your call or name in comment, it will be appreciated.
Deletehttps://www.news-medical.net/news/20201207/STE90-C11-a-SARS-CoV-2-neutralizing-antibody-shows-high-inhibition-of-RBD-ACE2-binding.aspx