Vitamin K3 and naphtoquinone-derivative as Covid-19 protease inhibitors

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This study found that vitamin K3 and certain other naphtoquinones are strong 3CL protease inhibitors. It is the main protease for coronaviruses and needed for viral replication. Thus could be highly beneficial as a treatment.
(3C-like protease - Wikipedia)

Vitamin K2 has been shown to have good binding affinity for the spike protein and has anti-viral activity as a quinone.
Unfortunately vitamin K2 did NOT work in this case, as it has a different structure.

"As thiol group of cysteine of SARS-CoV-2 3CLpro attacks the C3 position of Vitamin K3 to form the covalent bond, any bulky substitution at C3 will block the reaction. Analogues, such as Vitamin K1 and K2, have long alkyl chain substituents at C3 position, which do not form the covalent bond due to the steric hindrance."


They did however refine the molecule and looked what worked . And finally ended up with
5,8-dihydroxy-1,4-naphthoquinone, which is even more effective than K3.

"These results indicate that Vitamin K3 analogue 5,8-dihydroxy-1,4-naphthoquinone had stronger inhibitory activity and can also covalently bind to SARS-CoV-2 3CLpro as an irreversible inhibitor."

"Then we analyzed the structure-activity relationship of Vitamin K3 analogues and identified 5,8-dihydroxy-1,4-naphthoquinone with 9.8 times higher inhibitory activity than Vitamin K3."

5,8-dihydroxy-1,4-naphthoquinone,also known as Naphthazarin is an interesting compound and has anti-bacterial, anti-inflammatory and anti-tumor effects. It has also been studied as potential treatment for Parkinson's. (Error - Cookies Turned Off)

Identification of Vitamin K3 and its analogues as covalent inhibitors of SARS-CoV-2 3CLpro

After the emergence of the pandemic, repurposed drugs have been considered as a quicker way of finding potential antiviral agents. SARS-CoV-2 3CL[pro] is essential for processing the viral polyproteins into mature non-structural proteins, making it an ...

www.ncbi.nlm.nih.gov

 

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For those who are interested in naphthazarin: it isn't for sale ,unless you count sigma aldrich et. al, but there is a plant called red gromwell (Lithospermum erythrorhizon) that contains naphthazarin and shikonin, which is another interesting naphtoquinone (COX AND LOX inhibtor amongst other things.

Here's a few studies on shikonin/ Lithospermum erythrorhizon:

1.
"LE reduced high-fat diet-induced increases in body weight, white adipose tissue mass, serum triglyceride and total cholesterol levels, and hepatic lipid levels while decreasing lipogenic and adipogenic gene expression. Furthermore, acetylshikonin suppressed adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factor expression in 3T3-L1 cells."
(https://pubs.acs.org/doi/abs/10.1021/jf3017404#)

2.(Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo - PubMed)

3.(Shikonin, a constituent of Lithospermum erythrorhizon exhibits anti-allergic effects by suppressing orphan nuclear receptor Nr4a family gene expression as a new prototype of calcineurin inhibitors in mast cells - PubMed)

4.
(Shikonin changes the lipopolysaccharide-induced expression of inflammation-related genes in macrophages - PubMed)

5. (Shikonin attenuates acetaminophen-induced acute liver injury via inhibition of oxidative stress and inflammation - PubMed)

6.(Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis - PubMed)

 

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Shikonin for covid

(Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors - PubMed)

(Crystal structure of SARS-CoV-2 main protease in complex with the natural product inhibitor shikonin illuminates a unique binding mode - PubMed)

(Discovery of potent inhibitors for M pro enzyme of SARS-COV2 by multi-stage in-silico screening of Alkannin/shikonin - PubMed)

 

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Gromwell Root: A Natural Anti-Viral Ally - The Alchemist's Kitchen

Gromwell (Lithospermum erythrorhizon) is an herbaceous plant with potent medicinal properties, widely employed in modern and traditional Eastern healing practices. Gromwell root is the most commonly used part of the plant; the first recorded medicinal use of the root appeared in the ancient...

wisdom.thealchemistskitchen.com