NCBI Virus
NCBI Virus is a community portal for viral sequence data from RefSeq, GenBank and other NCBI repositories.
www.ncbi.nlm.nih.gov
in case anyone wants to analyze/make any notes. I'm using Ugene to analyze.
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Members of the previous forum can retrieve their temporary password here, (login and check your PM).
SARS-CoV-2 Sequences
- Thread starter benzyme
- Start date
www.ncbi.nlm.nih.gov
in case anyone wants to analyze/make any notes. I'm using Ugene to analyze.
JP
Rising Star
What are your thoughts on this?
www.researchsquare.com
www.ncbi.nlm.nih.gov
It seems we may be wrong about blocking the ACE2, and that HSP-90 inhibition is the real way to stop this demon (virus).
Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection
Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses (SARS-FCoVs); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset...
www.researchsquare.com
Harmine Is a Potent Antimalarial Targeting Hsp90 and Synergizes with Chloroquine and Artemisinin
Previous studies have shown an antimalarial effect of total alkaloids extracted from leaves of Guiera senegalensis from Mali in West Africa. We independently observed that the beta-carboline alkaloid harmine obtained from a natural product library screen ...
www.ncbi.nlm.nih.gov
It seems we may be wrong about blocking the ACE2, and that HSP-90 inhibition is the real way to stop this demon (virus).
sounds plausible.
the first article is interesting, not sure how I feel about the second.. administering a RIMA with a known hepatotoxin. :?:
the first article is interesting, not sure how I feel about the second.. administering a RIMA with a known hepatotoxin. :?:
With ACE-2 it depends:JP said:
[YOUTUBE]
Kind regards,
The Traveler
downwardsfromzero
Boundary condition
An interesting snippet to take away from the second paper (Harmine Is a Potent Antimalarial Targeting Hsp90 and Synergizes with Chloroquine and Artemisinin) 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
:
Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro "Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro"
A search indicates that Hsp90 shows promise as a target in various cancer therapies.
The same search turned up this: SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection - Nature Communications
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
:Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro "Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro"
Don't rush to stock up on geldanamycin just yet:
A search indicates that Hsp90 shows promise as a target in various cancer therapies.
The same search turned up this: SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection - Nature Communications
Tests using a soluble form of ACE2 to bind to the virus and lock it up look promising.
Press release: Trial drug can significantly block early stages of COVID-19 in engineered human tissues - UBC News
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
Press release: Trial drug can significantly block early stages of COVID-19 in engineered human tissues - UBC News
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
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.sciencedirect.com/science/article/pii/S0924857920301102
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.sciencedirect.com/science/article/pii/S0924857920301102
cave paintings
Rising Star
https://stm.sciencemag.org/content/early/2020/04/03/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.
"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.
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 :thumb_up:
"Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development"
chemrxiv.org
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 :thumb_up:
"Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development"
Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development
Spike glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I fusion protein which helps the virus in its initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with the host cells. The attachment is mediated by the S1 subunit...
chemrxiv.org
Hungarian researchers (not from my team) have come up with these:
www.webbeteg.hu
www.egeszsegkalauz.hu
I 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:
www.ncbi.nlm.nih.gov
According to them chloroquine also acts through the sigma-1 receptor.
Koronavírus: Főszerephez juthat a Sigma-1 receptor - WEBBeteg
A Sigma-1 receptor serkentése áttörést hozhat a koronavírus-megbetegedések szövődményeként kialakuló tüdőgyulladás és szöveti hegesedés kezelésében...
www.webbeteg.hu
Magyar kutatók szabadalma: a Sigma-1 molekula áttörést hozhat a koronavírus gyógyításában
Magyar kutatók jöttek rá, hogy a Sigma-1 nevű receptort már eleve meglévő gyógyszerrel is aktiválhatják, ennek pedig nagy jelentősége lehet a koronavírus kezelésében. A kutatók azon dolgoznak, hogy a szer mielőbb kipróbálható legyen a Covid-19-ben szenvedő betegeknél.
www.egeszsegkalauz.hu
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:
Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells - PubMed
The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo...
www.ncbi.nlm.nih.gov
Here is the announcement above in English:
If the haem hypothesis is valid, than the SigmaR-1 mediated antihypoxia effect (published by us) may also work as a second defense mechanism:
www.ncbi.nlm.nih.gov
If the haem hypothesis is valid, than the SigmaR-1 mediated antihypoxia effect (published by us) may also work as a second defense mechanism:
The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells - PubMed
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone...
www.ncbi.nlm.nih.gov
Fascinating!
I suspected something like this might be the case. Nice to see some elucidation of the potential mechanism.
Thanks for sharing this update. :thumb_up:
I suspected something like this might be the case. Nice to see some elucidation of the potential mechanism.
Thanks for sharing this update. :thumb_up:
..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 :thumb_up:
(and thanks all contributors to this thread, very helpful)
thank you for that work, and this new info! efrecska :thumb_up:
(and thanks all contributors to this thread, very helpful)
In this article we have addressed the potential SigmaR-1 mediated benefits (among other mechanisms as well) of ayahuasca against various diseases of civilization:
www.frontiersin.org
SigmaR-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):
www.ncbi.nlm.nih.gov
And SigmaR-1 is a nervous bookkeeper in maintaining order between them.
Frontiers | The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization
Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca i...
www.frontiersin.org
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):
molecular web: endoplasmic reticulum stress, inflammation, - Search Results - PubMed
molecular web: endoplasmic reticulum stress, inflammation, - Search Results - PubMed
www.ncbi.nlm.nih.gov
And SigmaR-1 is a nervous bookkeeper in maintaining order between them.
efrecska said:
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.
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.
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.