analytical chemist
   
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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https://www.ncbi.nlm.nih...genbank/sars-cov-2-seqs/in case anyone wants to analyze/make any notes. I'm using Ugene to analyze. "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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DMT-Nexus member
Posts: 118 Joined: 16-Sep-2017 Last visit: 30-May-2023
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What are your thoughts on this? https://www.researchsquare.com/article/rs-18714/v1https://www.ncbi.nlm.nih...pmc/articles/PMC3421604/It seems we may be wrong about blocking the ACE2, and that HSP-90 inhibition is the real way to stop this demon (virus). And you will come to find that we are all one mind
Capable of all that's imagined and all conceivable.
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analytical chemist
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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sounds plausible. the first article is interesting, not sure how I feel about the second.. administering a RIMA with a known hepatotoxin.  "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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"No, seriously"
Posts: 7324 Joined: 18-Jan-2007 Last visit: 02-Nov-2024 Location: Orion Spur
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JP wrote:It seems we may be wrong about blocking the ACE2, and that HSP-90 inhibition is the real way to stop this demon (virus). With ACE-2 it depends: Kind regards, The Traveler
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Boundary condition
Posts: 8617 Joined: 30-Aug-2008 Last visit: 07-Nov-2024 Location: square root of minus one
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An interesting snippet to take away from the second paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421604/) is that harman is an antimalarial agent. Hsp90 relates to the Plasmodium parasite that causes malaria; it seems (to me) unlikely to be involved coronavirus pathogenicity. Edit: hehe, I was clearly wrong  : https://www.ncbi.nlm.nih...pmc/articles/PMC353133/# "Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro" Quote:Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus. Don't rush to stock up on geldanamycin just yet: Quote:geldanamycin presents several major drawbacks as a drug candidate such as hepatotoxicity, further, Jilani et al. reported that geldanamycin induces the apoptosis of erythrocytes under physiological concentrations. A search indicates that Hsp90 shows promise as a target in various cancer therapies. The same search turned up this: https://www.nature.com/articles/s41467-019-13659-4Quote:Studies investigating the interplay between autophagy and viruses revealed that some viruses use parts of the autophagy machinery for their own replication but also have evolved strategies to escape autophagic degradation. Congruently, autophagy-inducing agents can have antiviral effects13. In case of coronaviruses (CoV), the formation of replication complexes at double membrane vesicles (DMV) and, most likely, of infectious particles depend on ER-derived membranes, as does autophagy14,15,16. Thus, current knowledge suggests that CoV interact differentially with components of the autophagic pathway with the potential for both the utilization of autophagy components for virus replication and for the attenuation of autophagy17. Substances inhibiting the generation of DMVs have been shown to be broadly reactive against CoV replication in vitro18. Importantly, this included CoV of different genera including the emerging Middle East respiratory syndrome (MERS)-CoV, a paradigmatic emerging virus that entails considerable pandemic risks due to its prevalence in dromedary populations in Africa and the Arabian Pensinsula and its transmission via the respiratory tract causing a severe form of pneumonia in humans. βThere is a way of manipulating matter and energy so as to produce what modern scientists call 'a field of force'. The field acts on the observer and puts him in a privileged position vis-à-vis the universe. From this position he has access to the realities which are ordinarily hidden from us by time and space, matter and energy. This is what we call the Great Work." β Jacques Bergier, quoting Fulcanelli
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β€οΈβ🔥
Posts: 3648 Joined: 11-Mar-2017 Last visit: 26-Nov-2024 Location: 🌎
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Details on ACE2 binding have been just published. "Structural basis of receptor recognition by SARS-CoV-2" Attaching paper.
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β€οΈβ🔥
Posts: 3648 Joined: 11-Mar-2017 Last visit: 26-Nov-2024 Location: 🌎
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Tests using a soluble form of ACE2 to bind to the virus and lock it up look promising. Press release: https://news.ubc.ca/2020...ngineered-human-tissues/Upcoming publication: Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Submitted to Cell, 2020 DOI: 10.1016/j.cell.2020.04.004
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β€οΈβ🔥
Posts: 3648 Joined: 11-Mar-2017 Last visit: 26-Nov-2024 Location: 🌎
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Molecular modeling research model indicates that hydroxychloroquine reduces SARS-CoV-2 ACE2 receptor affinity. Title: "Structural and molecular modeling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection" Open access: https://www.sciencedirec...le/pii/S0924857920301102
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DMT-Nexus member
Posts: 415 Joined: 10-Jul-2010 Last visit: 18-Apr-2020 Location: Earth
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https://stm.sciencemag.o.../03/scitranslmed.abb5883 "An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice" - published in Science. Full text is in link above. Living to Give
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β€οΈβ🔥
Posts: 3648 Joined: 11-Mar-2017 Last visit: 26-Nov-2024 Location: 🌎
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Interesting study from India on natural compounds that could have activity against the novel coronavirus via S1 or S2 virus spike glycoprotein site binding (as defined in the paper). In particular, several beat hydroxychloroquine in its S1 binding. Complete list is in the open access paper in the link below. You can find many of these phytochemicals in delicious things like beans, kale, brocolli, tumeric, strawberries, and tea. No in-vivo data yet, worst case you eat healthy  "Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development" https://chemrxiv.org/art...rug_Development/12094203
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I rather root my values in my own hallucinations than in society´s neurotic illusions..
Posts: 681 Joined: 08-Jul-2017 Last visit: 08-Jul-2020 Location: Barcelona
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Perfect, Im eating broccoli and strawberries daily  "Too cute to live, too cozy to die" - Eaglepath
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DMT-Nexus member
Posts: 21 Joined: 03-May-2013 Last visit: 24-May-2021 Location: Debrecen
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Hungarian researchers (not from my team) have come up with these: https://www.webbeteg.hu/...us-es-sigma-egy-receptorhttps://www.egeszsegkala...at-a-koronavirus/w998l6pI hope Google translator helps with it, or soon it will be over the net in English. Well, for my team this hasn't come as a surprise because we published in 2014 the sigma-1 receptor mediated antiinflammatory effect of DMT and 5-MeoDMT: https://www.ncbi.nlm.nih.gov/pubmed/25171370According to them chloroquine also acts through the sigma-1 receptor.
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DMT-Nexus member
Posts: 21 Joined: 03-May-2013 Last visit: 24-May-2021 Location: Debrecen
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Here is the announcement above in English: http://semmelweis.hu/eng...e-treatment-of-covid-19/If the haem hypothesis is valid, than the SigmaR-1 mediated antihypoxia effect (published by us) may also work as a second defense mechanism: https://www.ncbi.nlm.nih.gov/pubmed/27683542
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Dreamoar
Posts: 4711 Joined: 10-Sep-2009 Last visit: 21-Nov-2024 Location: Rocky mountain high
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Fascinating! I suspected something like this might be the case. Nice to see some elucidation of the potential mechanism. Thanks for sharing this update.
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member for the trees
 
Posts: 4003 Joined: 28-Jun-2011 Last visit: 27-May-2024
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..i was reading the paper with "sigma-1 receptor mediated antiinflammatory effect of DMT" in the past few days, and pondering mentioning that along with some flavonoid/IL-6 studies.. thank you for that work, and this new info! efrecska (and thanks all contributors to this thread, very helpful)
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DMT-Nexus member
Posts: 21 Joined: 03-May-2013 Last visit: 24-May-2021 Location: Debrecen
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In this article we have addressed the potential SigmaR-1 mediated benefits (among other mechanisms as well) of ayahuasca against various diseases of civilization: https://www.frontiersin....89/fphar.2016.00035/fullSigmaR-1 action alleviates various forms of cellular stress (ER, oxidative, mitochondrial stress, unfolded protein response) and works against apoptotic cell death. Well, for a while at least. Nevertheless, we don't want to state that every diseases of civilization comes from low SigmaR-1 expression. The concept is that SigmaR-1 agonism may serve some sort of buffering mechanism in the imbalance between the mitochondrion (the powerplant of the cell) and endoplasmic reticulum (the protein factory of the cell). Chronic low grade inflammation is a pretty common ground in a vast array of diseases (metabolic syndrome, neurodegenerative and psychiatric illnesses, dementias, etc.) and it manifests on the cellular level in a web of cellular stresses (see types above and a reference here): https://www.ncbi.nlm.nih...tress%2C+inflammation%2CAnd SigmaR-1 is a nervous bookkeeper in maintaining order between them.
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DMT-Nexus member
Posts: 21 Joined: 03-May-2013 Last visit: 24-May-2021 Location: Debrecen
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How complicated things are: Charles Nichols' lab has an unpublished in vitro study indicating that the cellular pathology of SARS-CoV2 was increased in the presence of psychedelics.
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DMT-Nexus member
Posts: 14191 Joined: 19-Feb-2008 Last visit: 28-Nov-2024 Location: Jungle
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efrecska wrote:How complicated things are: Charles Nichols' lab has an unpublished in vitro study indicating that the cellular pathology of SARS-CoV2 was increased in the presence of psychedelics. Do you have any info what psychedelics were (was?) tested, or direct contact with Nichols to ask? Someone mentioned this unpublished research before here in the forum and it seemed oddly vague to just say "psychedelics", given the pharmacological differences in different psychedelics. Also any info regarding concentrations used would be good too, and if there was a dose-dependent effect.
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DMT-Nexus member
Posts: 21 Joined: 03-May-2013 Last visit: 24-May-2021 Location: Debrecen
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I don't have yet the details.
Indeed, the type of the psychedelic, the dose, the timing, and the way of administration are very important factors. Especially in acute viral or bacterial infections. If they used DOI (their favorite) that is a very potent antiinflammatory agent via the 5-HT2A receptor (its sigma-1 receptor effect is unknown). Inflammation in infections is a totally different issue as compared to the chronic low-grade inflammation in the background of diseases of civilization. The latter is entirely pathological. In infections inflammation is adaptive, only the acute very high-grade form (cytokinestorm) can be gravely problematic.
In COVID cases with lung and other organ complications antiinflammatory effect can be beneficiary against the cytokinestorm (timing is critical though: not too early, not too late). Probably not with DMT: I reserve (and study) it for cardiopulmonary resucitation, traumatic brain injury, neuroinflammation, and against ischemic-reperfusion injury.
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β€οΈβ🔥
Posts: 3648 Joined: 11-Mar-2017 Last visit: 26-Nov-2024 Location: 🌎
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endlessness wrote:efrecska wrote:How complicated things are: Charles Nichols' lab has an unpublished in vitro study indicating that the cellular pathology of SARS-CoV2 was increased in the presence of psychedelics. Do you have any info what psychedelics were (was?) tested, or direct contact with Nichols to ask? Someone mentioned this unpublished research before here in the forum and it seemed oddly vague to just say "psychedelics", given the pharmacological differences in different psychedelics. Also any info regarding concentrations used would be good too, and if there was a dose-dependent effect. Here is that mention along with some personal user reports.
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