Proteases Puns

Todos Medical and NLC Pharma Announce Primary and Secondary Endpoints Met in NLC-V-01 Phase 2 Clinical Trial of Oral Antiviral 3CL Protease Inhibitor Tollovir™ in the Treatment of Hospitalized COVID-19 Patients :: Todos Medical Ltd. (TOMDF)

§  Phase 2 Study NLC-V-01 closed early after interim data analysis due to positive clinical efficacy

§  Primary endpoint of time to clinical improvement reached with average reduction of 2.7 days in the Tollovir group vs. the placebo group

§  0% COVID-related deaths in Tollovir™ group vs. 22% COVID-related deaths in placebo group

§  Lead clinical site Shaare Zedek Medical Center now permits the use of Tollovir™ in hospitalized COVID-19 patients on a compassionate use basis

§  Company preparing Phase 2/3 clinical trial to support Emergency Use Authorizations

§  Company to host conference call today at 9:15am ET to discuss the positive Phase 2 trial results

§  Company to make a corporate presentation for Emerging Growth Conference today at 3:00pm ET

New York, NEW YORK, and Tel Aviv, ISRAEL, Jan. 27, 2022 (GLOBE NEWSWIRE) -- via NewMediaWire --Todos Medical, Ltd. (OTCQB: TOMDF), a comprehensive medical diagnostics and related solutions company, together with its 3CL protease theranostic joint venture partner NLC Pharma Ltd., today announced positive interim data for its Tollovir™ oral antiviral 3CL protease inhibitor Phase 2 clinical trial for the treatment of hospitalized (severe and critical) COVID-19 patients. Tollovir met its primary endpoint of reducing time to clinical improvement as measured by the National Emergency Warning System 2 (NEWS2) and met several key secondary clinical endpoints, including complete reduction in COVID-19 deaths. The Company has now formally closed the Phase 2 clinical trial due to positive interim efficacy data. Lead clinical site Shaare Zedek Medical Center now permits the use of Tollovir™ in hospitalized COVID-19 patients on a compassionate use basis.

The Company will host a conference call at 9:15am Eastern Time. The conference call link is: [https://audience.mysequire.com/webinar-view?webinar_id=cd68df03-4911-4ded-a910-ba73d61afeeb](https://www.globenewswire.com/Tracker?data=LRMUkCS

The satiety index of potatoes is not predicted by its glycemic index, glycemic load, or protein and water content. The disproportionately high satiety index of potatoes is thought to be due to protease inhibitors. PL2 was thought to be the primary mediator of this action in potatoes but this paper shows that PL2 is less satiety-inducing than equal quantities of other protease inhibitors found in potatoes. Note that PL2 is only 5% of the protein content in potatoes.

The same paper found that non-isolated protease inhibitors in potatoes showed less detrimental effects (impairing protein intake, tumor genesis, etc).

I can't seem to find any further research utilizing non-isolated proteases from potatoes, only PL2 studies.

It would be interesting to see non-isolated potatoes proteases used in a medical intervention for wieght loss.

Thoughts?

wouldn't the SDS/boiling get rid of any proteases?

https://investors.sorrentotherapeutics.com/news-releases/news-release-details/sorrento-announces-its-oral-sars-cov-2-main-protease-mpro

https://www.nature.com/articles/s41598-020-63438-1#Sec2

It's a very long winded read and hard to surmise the results in vero (cultured human and primate cells) but is stated as a possible novel antiviral for treatment of HSV.

Maybe some of you with a medical background could evaluate this paper better than me.

“Development, validation, and approval of COVID-19 specific drugs takes years1. Therefore, the idea of drug repositioning, also known as repurposing, is an important strategy to control the sudden outbreak of life-threatening infectious agents that spread rapidly.”

https://pubs.rsc.org/en/content/articlehtml/2021/cp/d1cp02967c

https://www.nature.com/articles/s42003-020-01577-x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996102/

https://www.frontiersin.org/articles/10.3389/fmicb.2020.592908/full#h1

A rapid colorimetric detection of SARS-CoV-2 protease using a zwitterionic peptide and gold colloids is reported. The sensor showed good performance in exhaled breath condensate with a limit of detection in the low nanomolar range. This technology can be integrated into regular face coverings for COVID-detection.

Abstract

The transmission of SARS-CoV-2 coronavirus has led to the COVID-19 pandemic. Nucleic acid testing while specific has limitations for mass surveillance. One alternative is the main protease (Mpro) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect Mpro via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C-/N-terminus to exploit the specific recognition by Mpro. Autolytic cleavage releases a positively charged moiety that assembles the nanoparticles with rapid color changes (tpro in breath condensate matrices

https://ift.tt/3ej8nmR

Abstract

A number of inhibitors have been developed for the SARS-CoV-2 main protease (MPro ) as potential COVID-19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition of TMPRSS2, furin, and cathepsins B/K/L by more than a dozen of previously developed MPro inhibitors including MPI1-9, GC376, 11a, 10-1, 10-2, and 10-3. MPI1-9, GC376 and 11a all contain an aldehyde for the formation of a reversible covalent hemiacetal adduct with the MPro active site cysteine and 10-1, 10-2 and 10-3 contain a labile ester to exchange with the MPro active site cysteine for the formation of a thioester. Our data revealed that all these inhibitors are inert toward TMPRSS2 and furin. Diaryl esters also showed low inhibition of cathepsins. However, all aldehyde inhibitors displayed high potency in inhibiting three cathepsins. Their determined IC50 values vary from 4.1 to 380 nM for cathepsin B, 0.079 to 2.3 nM for cathepsin L, and 0.35 to 180 nM for cathepsin K. All aldehyde inhibitors showed similar inhibition levels toward cathepsin L. A cellular analysis indicated high potency of MPI5 and MPI8 in inhibiting lysosomal activity, which is probably attributed to their inhibition of cathepsins. Among all aldehyde inhibitors, MPI8 shows the best selectivity toward cathepsin L. With respect to cathepsins B and K, the selective indices are 192 and 150, respectively. MPI8 is the most potent compound among all aldehyde inhibitors in cellular MPro inhibition potency and anti-SARS-CoV-2 activity in Vero E6 cells. Cathepsin L has been demonstrated to play a critical role in the SARS-CoV-2 cell entry. By selectively inhibiting both SARS-CoV-2 MPro and the host cathepsin L, MPI8 potentiates dual inhibition effects to synergize its overall antiviral potency and efficacy. Due to its high selectivity toward cathepsin L that reduces potential toxicity toward host cells and high cellular and antiviral potency, we urge serious consideration of MPI8 for preclinical and clinical investigations for treating COVID-19.

https://pubmed.ncbi.nlm.nih.gov/34242492/

In laymen's terms IT WORKS AGAINST ALL VARIANTS.