COVID-19 Latest: More Antibody Resistant SARS-CoV-2 Mutated Strains Emerging And Increasing In Circulation!

A new study by researchers from the Department of Microbiology and Infectious Disease Center, Peking University Health Science Center-Beijing has alarmingly identified a growing number mutated strains of the SARS-CoV-2 coronavirus that is antibody resistant.


 
The research findings were published in the peer-reviewed journal: Nature’s
Signal Transduction And Targeted Therapy https://www.nature.com/articles/s41392-020-00302-8
 
The study team investigated 80 natural variants and 26 glycosylation-spike (S) mutants of SARS-CoV-2 in terms of infectivity and antigenicity.


Schematic illustration of amino acid changes in spike protein. Mutations yielding at least fourfold changes in infectivity and neutralizing reactivity to mAbs are shown in the figure

Alarmingly the study team identified several mutations that can critically affect the SARS-CoV-2 coronavirus infectivity and reactivity to neutralizing antibodies. (in this article however we will only be focusing on the antibody resistance aspects)

Impact of mutations in S protein:

The research findings have enormous implications on the impact of mutations in S protein on current vaccine candidates and monoclonal antibodies (mAbs).
 
In order to investigate the antigenicity of the infectious mutants, the study team used 13 neutralizing mAbs.
 
Significantly the researchers discovered ten mutations, such as N234Q, L452R, A475V, V483A, and F490L, which were remarkably resistant to some of the mAbs.
 
The other identified strains also antibody resistant were N439K, A831V and Y508H.
 
Two more strains that were of concern were additional mutations found on certain variants of the now dominant mutated strain that is prevailing ie the D614G strain. These variants were identified as D614G+A435S and D614G+I472V.
 
Interestingly most of the mutations located in the RBD.
 
Simply by analyzing the epitope of three well-characterized mAbs, P2B-2F6, CB6, and H014 on the trimer and RBD, the researchers discovered that several variants that are resistant to these mAbs sit in the binding epitope of RBD.
 
Importantly the results of the neutralizing assay using human convalescent sera were mostly consistent with mAbs, and the differences of neutralization activity, though less than fourfold, were statistically significant. This part of the study is of great importance for vaccine and mAb therapy development as it provides evidence of how circulating natural variants react to neutralizing antibodies.
 
Desirable vaccine candidates or mAbs should have broad-spectrum reactivity to neutralize all circulating variants. (none of the current vaccin es developed or are in phase 3 trials meet this criteria)
 
Also, development and design of cocktail therapy combining two or more mAbs that can target all mutations may be of particular interest in the future.
 
It should be noted that there is currently a concerted effort to downplay or even censor any mention about mutated strains that are antibody resistant by certain vested parties with huge pockets of monies.
 
We still have many journalist who claim to be science writers still writing in various publications and claiming that the SARS-CoV-2 coronavirus is not mutating or that even if it is mutating , we have nothing to worry about as they claim it is only decreasing in potency and we also have some stupid virologist making such claims when they are not involved in any genomic tracking studies and do not have a real sense of what is happening.
 
Thailand Medical News has already warned about the V483G strain that is increasing in circulation. https://www.thailandmedical.news/news/v483g-mutation-warning-about-growing-prevalence-of-new-sars-cov-2-mutant-strain-v483g-that-is-antibody-resistant-and-even-more-infectious
 
The V483G strain is highly antibody resistant and is more potent and infectious but what is worrisome is that it is becoming more prevalent in the United States. In May 2020, the V483A strain exceeded 0.1% in frequency of all of which were found in the United States, with 28 sequences reported as of May 6, 2020, and 36 up to July 3, 2020.  https://www.cell.com/cell/pdf/S0092-8674(20)30877-1.pdf

Alarming this mutated sequence is popping up more in various counties in the Mid-Western states and also in the Northwestern states of America. Sources are reporting that this frequency has now increased to 3.7 percent in September 2020 but the U.S.CDC and U.S. NIH are concealing data despite many parties asking for clarifications of this.
 
Should one use existing modeling platforms, this strain could be a major prevailing strain in the United States by as early as late-December! , accounting for almost 50 percent for all new infections!
 
The repercussions of antibody strain being prevalent and the implications of the vaccines and antibody treatments under development or clinical trials is phenomenal.

Antibody resistant strain:

Importantly another mutation the A475V strain that is also antibody resistant strain also had an initial frequency of more than 0.1% in both UK and The US in May 2020 and is also increasing in circulation. https://www.cell.com/cell/pdf/S0092-8674(20)30877-1.pdf
 
Both the V483G strain and A475V strains are not the only threat.
 
The growing number of variants of the current global dominant strain ie the  D614G strains with additional mutations on them  for example the D614G strain with a I472V mutation on it that is also fast growing in the United States and Europe. This strain is not only more antibody resistant and infectious https://www.cell.com/cell/pdf/S0092-8674(20)30877-1.pdf but there are now studies underway that indicate that it might also be resistant to T Cells! (A supporting preprint study on this will be published soon.)
 
There are other D614G variants identified in the US that are not only more infectious but also but also now believed to be also said to be resistant to the immune  functions of the human host.
https://www.thailandmedical.news/news/breaking-covid-19-latest-us-study-shows-co-infection-with-two-different-strains-of-sars-cov-2-is-more-deadly-and-more-such-cases-emerging-globally
 
There are now almost 17 such D614G variants emerging including one in India that has emerged in the state of Gujerat that has been found to be highly lethal. https://www.researchsquare.com/article/rs-90273/v1...... ( A D614G mutation variant with 2 other mutations on it!)…we will covering details on this in a separate article as we obtain more information)

Study by researchers: 

In another study by researchers from  IBM TJ Watson Research Center lead by Dr Takahiko Koyama, a genomic and virology specialists that was also published in the WHO (World Health Organization) research bulletins, https://www.who.int/bulletin/volumes/98/7/20-253591/en/ or https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375210/
the researchers warn of not only antibody strains developing but also of drug resistant strains ie, “Almost all strains with D614G mutation also have a mutation in the protein responsible for replication (ORF1ab P4715L; RdRp P323L), which might affect replication speed of the virus. This protein is the target of the anti-viral drugs, remdesivir and favipiravir, and the susceptibility for mutations suggests that treatment resistive strains may emerge quickly. Mutations in the receptor binding domain of the spike protein suggest that these variants are unlikely to reduce binding affinity with ACE2, since that would decrease the fitness of the virus. V483A and G476S are primarily observed in samples from the United States, whereas V367F is found in samples from China, Hong Kong Special Administrative Region, France and the Netherlands. The V367F and D364Y variants have been reported to enhance the structural stability of the spike protein facilitating more efficient binding to the ACE2 receptor. In summary, structural and functional changes concomitant with spike protein mutations should be meticulously studied during therapy and vaccine design and development.”
 
Despite warnings as early as February with the study revised and published in June, no vaccine developers took much heed when developing the first generation of vaccines we have in phase 3 trials at the moment.
 
We have some of the vaccine developers saying that the mutations will not affect the vaccines that were developed using the initial Wuhan strains despite facts showing otherwise plus they do not have any supporting studies to back their claims.
 
Recently there were some manipulated ‘half-baked ‘studies from Australian researchers who are not involved in the vaccine developments but were most probably ‘paid’ to come up with silico and animal model studies using ferrets to claim that the vaccines would still be effective on the D614G strain despite no mention being made in their reports about the other emerging strains including V483G strain or the new D614G variants with more mutations on it that are fast increasing in frequency and circulation.
 
Thailand Medical News will continue to report of new developments on these emerging antibody strains and also the frequency and circulation trends of these strains despite being warned against reporting on this area by certain American entities.
 
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