The latest Investing Matters Podcast episode featuring Jeremy Skillington, CEO of Poolbeg Pharma has just been released. Listen here.
London South East prides itself on its community spirit, and in order to keep the chat section problem free, we ask all members to follow these simple rules. In these rules, we refer to ourselves as "we", "us", "our". The user of the website is referred to as "you" and "your".
By posting on our share chat boards you are agreeing to the following:
The IP address of all posts is recorded to aid in enforcing these conditions. As a user you agree to any information you have entered being stored in a database. You agree that we have the right to remove, edit, move or close any topic or board at any time should we see fit. You agree that we have the right to remove any post without notice. You agree that we have the right to suspend your account without notice.
Please note some users may not behave properly and may post content that is misleading, untrue or offensive.
It is not possible for us to fully monitor all content all of the time but where we have actually received notice of any content that is potentially misleading, untrue, offensive, unlawful, infringes third party rights or is potentially in breach of these terms and conditions, then we will review such content, decide whether to remove it from this website and act accordingly.
Premium Members are members that have a premium subscription with London South East. You can subscribe here.
London South East does not endorse such members, and posts should not be construed as advice and represent the opinions of the authors, not those of London South East Ltd, or its affiliates.
For those perhaps concerned about targeting the S protein in Avacta LFT listen to the scientist involved may help in understanding the benefits . .
Courtesy of tweet Lee W aka Poirot
https://twitter.com/lee_williams97/status/1464649533133107204
"Very good chance AffiDX will detect the new variant imo.
As Affimers are NOT generated by an animals immune response, they tend to bind to regions that don’t mutate or those that antibodies look for.
Dr Matt Johnson from #AVCT 57.40 minutes in…..
https://avacta.wistia.com/medias/75lszkgp3v?hss_channel=lcp-3342419
Muck, I’m guessing they’re saying that rather than bind to a random part of the spike protein, their test’s binders mimic the human cell ACE-2 receptors that the virus uses for entry. Since it needs to maintain this function to replicate (or else mutate into something completely different), it will continue to bind to the test.
But I don’t buy their claim that this means the test will get more accurate over time. The virus evolution is not driven solely by finding more efficient ways to enter the cell. Bigger drivers for it might be more efficient transmission from person to person, as well as vaccine escape and resistance to neutralising antibody therapies, and these could include compromises on other functions.
Or just very clever marketing?
My belief is that this is a clever way of saying their test detects the Spike protein, and not the N.
“ The proprietary Know Now® test, detects the spike protein to the virus (not the nucleocapsid protein as with all other lateral flow antigen tests) and this spike is only apparent on live virus, therefore the test only identifies those people with current infection. It is a true infectivity test.”
Sounds very good tech; they use a human cell instead of an affimer to bind though I imagine the sample could not be subjected to a buffer to make the virus inert if it has to do its thing. Any improved variant must bind better to the human cell so no need to rejig the binder/human cell. It has been around a while;21/12/20 ; " its technology works as a trapdoor using COVID-19 virus’ own mechanism of cell entry to generate signal. All the other antigen tests work by identifying the nucleocapsid protein in the centre of the virus, which is not a real measure of infectivity. " https://www.uktech.news/news/covid-19-20201221
Chill Olly - it’ll be fine.
There is no point to that apart from wasting time and money. The best we can hope for is positive evaluation from Europe and having that springboard to produce a pregnancy test and all the other markets to aim for.
Just a question. Vatic is the only other spike test I know, and they make this claim on LinkedIn;
“Because our test mimics a human cell, we are in fact seeing the more dominant strains mutate towards better binding affinity between the cell invasion mechanism of the virus and the surface of a human cell, precisely because it plays a role in making the virus more effective at entering cells, which impacts on its replication capabilities and thereby infectiousness”.
“The KnowNow Spike Test uses the same principle as the viral entry on a lateral flow assay platform to detect the virus. In our case as the virus mutates and becomes more infectious, our test should get more sensitive”
I’ll just own up and admit I don’t understand this. I would have thought they must have an assay which attaches somewhere in the spike like us, so why do they seem unconcerned with spike variants? Or is it BS?
Thanks for any help.
I just hope we are not going to be sidelined again and have to switch to the n protein to meet an ever changing government standard.
We know the N protein tests are ineffective at stopping spread so whether ours works or not it should be on the market. How will the powers that be defend themselves when eventually it is proved our test could have saved lives?
Our test is likely to work, just as it did with delta, which we validated against. Don’t forget, delta had mutations in the n and s areas. We will, and should validate against Omicron.
Thanks. I agree our test will work. But so often we see the governments following knee jerk reactions and setting policy based on perceptions. It’s concerning that they are excluding s protein tests.
Our test works when the virus is active and affimers bind in the region of the spikes not with the spikes. The N protein on its own is not infectious as it is spikes that attach to a host target and the N protein is not necessarily present in an active infection whereas the S protein when on the envelope of the active virus is the infectious virus stage which the AffiDX® SARS-CoV-2 Antigen Lateral Flow Test is designed to detect.
Virus Genomic Structure
The current COVID-19 pandemic is caused by the novel coronavirus strain SARS-CoV-2, a positive-sense, single-stranded enveloped RNA belonging to the Coronaviridae family12 (Figure 1A). The SARS-CoV-2 genome is >30 kb in length and consists of 14 open reading frames (ORFs) encoding 27 proteins.13 The 5' end of the SARS-CoV-2 genome consists of ORF1a/b encoding a polyprotein that is post-translationally cleaved into 16 non-structural proteins (nsp1–16), which form the replicase/transcriptase complex (RTC). This complex contains enzymes involved in the replication mechanism, including papain-like protease (nsp3), main protease (nsp5), nsp7-nsp8 primase complex, primary RNA-dependent RNA polymerase (RdRp; nsp12), helicase/triphosphatase (nsp13), exoribonuclease (nsp14), endonuclease (nsp15), and N7- and 2'-O-methyltransferases (nsp10/nsp16). The 3' terminus of the viral genome contains ORFs encoding the four main structural proteins, spike (S), envelope (E), membrane (M), and nucleocapsid (N), as well as nine putative accessory factors (Figure 1B).14,15https://www.dovepress.com/cr_data/article_fulltext/s306000/306441/img/IDR_A_306441_O_F0001g.jpg
Worth reading this thread with the images, very well explained why our test would detect it and also worth remembering that Al has previously said that because of the region we bind to there shouldnt be any problems (if needed they can just develop a new affimer and slot it in within a few weeks)
https://twitter.com/Ophidian18/status/146473641159315046
I hoped someone would disprove my theory there. The problem also could be even if we get HUA the fact it’s a s protein test may mean our tests cannot be used for flights etc because of concerns of the Omicron variant and the fact it mutates on the s spike. I would like someone to show me I’m talking rubbish with this theory please?
Validation batches sent to PD will not be relevant for EU notified body who maybe accept different route.
I think Medusa have been doing the field test for a year already and assume that is the evidence for HUA.
*in-vitro
Yes the b-vitro tests but our HUA will be field tested.
They all use Ehrlich, a shoe in for the EU list https://www.pei.de/DE/newsroom/dossier/coronavirus/coronavirus-inhalt.html;jsessionid=04E55676A371143BF675C2E00C632EE0.intranet232?nn=169730&cms_pos=8
Each member state will make its own choice as to what it uses. No mention of N or S protein target.
https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_en.pdf
If AffiDX® SARS-CoV-2 Antigen Lateral Flow Test could be validated in US that is another route. It is only a test, will not hurt anyone and should just be allowed to sell if it does the job. Would have saved lots of lives. The regulators have allowed vaccines because they do the job because the bigwig scientists OKed them and bigpharma saw the gravy train. Our test would not hit their bottom line but stoke a rival potential world pharma biotech company.
All are nucleocapsid, an independant validation study needs to bypass Paul-Ehrlich-Institut (https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_en.pdf ) and not use Roche( https://diagnostics.roche.com/global/en/products/systems/cobas_-8100-automated-workflow-series.html ) which may disadvantage the spike protein. It is a great opportunity for a rival validation service to claim the space in Europe with a better test to Ehrlich validated ones.
I have even wondered if the delay is because we have changed our test to include or be N protein.
Not much point in providing a test however good it is, if no one will accept it.
Can't see how we get EU approval if France bans it?
Can it get EU approval but then not be allowed to sell in an EU country?
Its a mystery....
Is the fact that we are targeting the s protein going to count against us as it appears that France and the U.K. don’t want s protein tests. Does the fact we are not on today’s revised list mean we are going to encounter this attitude towards s protein in Europe in general?