one toke

It’s been established that smoking wards off coronavirus (1 ,2), although that fact has not been widely promulgated.  Could you be protecting yourself even better if you were smoking dope?  I apologize if this is old news.  Two days old to me, which is when my dear friend and high school classmate in Houston sent me this news item about a finding out of Oregon State University (3).

In a diligent collaboration between researchers at the “Global Hemp Innovation Center” and the “Linus Pauling Institute” (who can beat that combo?!), came this discovery.  It’s well known that cannabis sativa contains a myriad of biologically active molecules.  Thanks for the THC, but there’s way more.  The class known as the cannabinoids must be important, as our brains and other cells have receptors for them.

What these folks ended up with was really a beautiful piece of work.  They stated a bit of their driving philosophy in the intro: “Natural products are the most successful sources of drugs and drug leads in the history of pharmacology.  Although combinatorial chemistry receives more emphasis for lead discovery by the pharmaceutical industry, nature continue to be a source of unique structural diversity for new drug discovery.”  So true.

Their search benefited from prior investigations that defined the battleground.  Infection by coronavirus begins by the attachment of the virus through the receptor binding domain (RBD) for the S1 subunit of the spike protein (residues 331-524) to the host receptor ACE2 on the outer membrane of cells, not just in lungs, but on arteries, heart, kidneys, and intestines.  Yes, they really do know this stuff down to the last molecule.

So, anything that gets in the way of this interaction would be a good thing.  It’s what those experimental mRNAs try to coax out in the form of antibodies to the spike, which get ever more ineffective as the spike continues to mutate beyond the original SARS-CoV-2 strain that provided the RNA..

So what these Beavers (Oregon State’s mascot) did was take a shotgun approach.  Thinking there must be something in this weed that would work, they employed a method called MagMASS in which they basically put the S1 component of spike protein on a bead and ran through stuff to see what would stick.  Many things did not, including THC, but 2 cannabinoids bound quite tightly: CBGA (cannabigerolic acid: tetrahydocannbinolic acid, THCA-A) and CBDA (cannibidiolic acid).  After that “aha” moment, the investigators showed the structural similarity of these compounds to the spike protein binding site, showed that these compounds blocked entry of SARS-CoV-2 into cultured cells, and showed this same blockage to variants B.1.1.7 (alpha) and B.1.351 (beta).

There are several pretty pictures in their paper.  I like this one which show how the cannabinoids bind snugly to the spike protein. Take that, Mr. Corona!

So what happens next?  Can stoners waive this paper at the COVID nazis demanding to see their vaxx passport?  At the very least, such preparation might make such oppression feel a little more tolerable.  Hey, what have you got to eat?  But seriously folks, there is more work to do.  What concentration of CBDA and CBGA needs to be attained at the alveolus to achieve relevant blocking?  How does that compare to the levels attained by smoking a regular joint?  Such data are attainable although I could only find the means, not the end (5).  Fortunately, CBDA is the most abundant cannabinoid in hemp (6). Concentrations of both CBDA and CBGA vary from strain to strain (7). One could see a route by which the OSU researchers patent the compounds, or at least the delivery system, and leave us with some sort of inhaler, costing God knows how much. A combo product with tobacco has some appeal, with perhaps some synergy between the anti-COVID compounds from each leaf. Not to be too blunt (8). With tinkering with marijuana’s genes a reality, and continuing to advance (9), producing a strain that makes only CBDA and CBGA should be feasible. Coronavirus protection without the buzz. Where’s the fun in that?

And time for our epidemiologist buddies to kick into gear!  There are now 28 states where marijuana use is either fully legal or significantly decriminalized.  How are those states doing with their COVID compared the other backward knuckle draggers?

While we wait for the data to roll in, seems to be a way forth https://www.youtube.com/watch?v=MNKL9onYB_8

You always knew it was good for you.

References

1.         Ike B.  Smokin’ corona.  WordPress. 2020 March 18. https://theviewfromharbal.com/2020/03/18/smokin-corona/

2.         Ike B.  smoke ‘em if you got ‘em?  WordPress. 2020 April 23. https://theviewfromharbal.com/2020/04/23/smoke-em-if-you-got-em/

3.         News staff.  OSU study: Compounds in hemp block COVID-19 from entering human cells.  KVAL 13. January 11, 2022.   https://kval.com/news/local/osu-study-compounds-in-hemp-could-block-covid-19-from-entering-human-cells?fbclid=IwAR2i9prcOU0Bl3mMv_lvvSYMFseh2_ar8puP4AV01UzW3-ofCkGK6Xe6gNE

4.         van Breemen RB, Muchiri RN, Bates TA, Weinstein JB, Leier HC, Farley S, Tafesse FG. Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants. J Nat Prod. 2022 Jan 10. doi: 10.1021/acs.jnatprod.1c00946. Epub ahead of print. PMID: 35007072. https://pubs.acs.org/doi/10.1021/acs.jnatprod.1c00946

5.         Fundación canna.  Quantification of the concentration of THC, CBD, CHG, THCA, CBDA, CBGA, THC total, CBDTotal, CBGTotal in HPLC. https://www.fundacion-canna.es/en/quantification-concentration-thc

6. Formato M, Crescente G, Scognamiglio M, Fiorentino A, Pecoraro MT, Piccolella S, Catauro M, Pacifico S. (‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research. Molecules. 2020 Jun 5;25(11):2638. doi: 10.3390/molecules25112638. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321064/

7. Coogan, T.A. Analysis of the cannabinoid content of strains available in the New Jersey Medicinal Marijuana Program. J Cannabis Res 111 (2019). https://doi.org/10.1186/s42238-019-0011-z

8. Hitt C. The tightly-rolled history of the blunt. Thrillist. 2020 August 21. https://www.thrillist.com/news/nation/what-is-a-blunt-history-origins-timeline

9. Long A. Genetic editing offers marijuana and hemp companies a way to improve plant strains. MJBizDaily. 2021 February 23 (updated 2021 December 17). https://mjbizdaily.com/genetic-editing-offers-marijuana-and-hemp-companies-a-way-to-improve-plant-strains/

Published by rike52

I retired from the Rheumatology division of Michigan Medicine end of June '19 after 36 years there. Upon hitting Ann Arbor for the second time (I went to school here) it took me almost 8 months to meet Kathy, 17 months to buy her a house (on Harbal, where we still live), and 37 months to marry her. Kids never came, but we've been blessed with a crowd of colleagues, friends, neighbors and family that continues to grow. Lots of them are going to show up in this log eventually. Stay tuned.

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