I was looking at the newspaper and there was a story about a corona , oral treatment drugs. In the past, there was a vaccine for influenza as well as a vaccine, and apart from that, there are medications such as Tamiflu and Relenza.
I have been calculating the HSP (Hansen Solubility Parameters) of such drugs.
In the same way, let’s calculate the HSP of the newly discovered oral treatment drugs for COVID-19 mild stage.
I will also include the SMILES structural formula so that people who have HSPiP can calculate it.
Molnupiravir(Merck): CC(C)C(=O)OCC2OC(n1ccc(=NO)[nH]c1=O)C(O)C2O
AT-527（Roche): CNc1nc(N)nc2c1NCN2C4OC(COP(=O)(NC(C)C(=O)OC(C)C)Oc3ccccc3)C(O)C4F
S-217622(Sionogi): COc4cccc5[nH]c(C(=O)NC(CC(C)C)C(=O)NC(CC1CCNC1=O)C(=O)c3nc2ccccc2s3)cc45
PF-07321332(pfizer): CC(C)(C)C(NC(=O)C(F)(F)F)C(=O)N1CC3C(C1C(=O)NC(C#N)CC2CCNC2=O)C3(C)C
Baricitinib : CCS(=O)(=O)N4CC(n3cc(c1ncnc2[nH]ccc12)cn3)C4CC#N
Recently, I have been thinking that most of these compounds should be divided into three structures.
The reason for the division of the drug structure into three parts.
The basic principle of Hansen Solubility Parameters (HSP) is that “like dissolves like”.
The average value of the entire molecule is not very meaningful.
If you want to get Smiles with your compound divided into several parts, see this blog.
The electron accepting (EA) and electron donating (ED) properties are also important for QSAR, so I will include the results of these calculations.
It’s interesting because the over all HSPs are quite similar.
| name | dD19 | dP19 | dH19 | dHAcid16 | dHBase16 | ElectronDonor | ElectronAcceptor |
| Molnupiravir | 18.86 | 9.27 | 13.49 | 8.49 | 19.67 | 15.6 | 21.3 |
| AT-527 | 20 | 10.69 | 10.35 | 6.26 | 16.57 | 32.2 | 24 |
| Y H-53 | 20.07 | 13.2 | 9.84 | 6.84 | 10.17 | 30.5 | 27.2 |
| PF-07321332 | 18.24 | 12.67 | 7.68 | 5.66 | 7.04 | 30.5 | 27.2 |
| Baricitinib | 20.65 | 11.35 | 8.26 | 3.46 | 9.91 | 20.7 | 25.5 |
I’m a little concerned about the small dH of the drug compared to the HSP of Corona.
Paxilovid is a fixed-dose combination of an antiviral drug (PF-07321332) and an anti-HIV drug, Ritonavir.
To calculate such a combination of Drugs, read this blog.
HSP Calculation for coronaviruses
Using HSPiP software, we can determine the HSP of a solute by doing a dissolution test using a solvent with known HSP.
Similarly, if we have the binding energy values of the virus and the compound, we can determine the HSP of each part of the virus.
The Omicron strain has 30 mutations that have never been seen before, and that conventional vaccines and antibodies may not work.
“How do I determine the solubility of the spike part?” was explained.
In fact, the parameters for this HSP calculation are not yet available (ver. 2019).
I’ve been working on ver. 2021 every day for a while now. I’m getting bored with it, so I did some calculations just for fun.
I’m asking CLI license users and other limited users to start using it for testing. We’ll release it after some more refinement.
If you are CLI license user and want to design new Drug for Omicron strain, please read the bioequivalence design page.
When I sent this page to Dr. Hansen, I received the following reply.
Back in 2008 I did get something similar published. The attachment finally got through the review process after some help from a certain Prof. Steven Abbott. It is his title, for example. Well anyway, I correlated the HSP for the chemotherapy drugs and got a very good HSP sphere out of it later. An average HSP for the DNA bases was 18.3, 10.3, 12.3. I think these are not too different from what you report. This HSP would also suffice for what it necessary for getting through cell walls, since these drugs just get in the way for reproductive processes at the DNA base sites (where the HSP match is good). The article has gotten 33 citations according to Google Scholar. Some time later I heard a talk where the speaker got a large molecule through cell walls by attaching to one or both ends what my memory says was DOX (Doxrubricin). This could get into the cell wall, and the rest could worm through afterwards. The point I have speculated on has been just how the cell walls are passed by virus. I know the receptor is there, but is it necessary if a part of the virus has the right HSP? I wish I could find someone to discuss this with, but either of you are welcome to pursue if you so choose.
In parentheses, which I use too many of, I had a project with a potential drug for psoriasis many years ago. I had it measured at FORCE. I had calculated the HSP and those measured were only off by 1 or 2 units. I resembled DOX with several rings, and had one OH group less, as I remember. I was very pleased with the calculation. I add this since what you are doing with the Y-MB are basically what I did back then by hand. About one hour for each chemical trying different ways to get at it.