We all are aware of SARS CoV 2 virus and its line of treatment by now. We are well aware targets for the SARS CoV 2 treatment which includes spike protein, Main Protease, RdRp. My team has found 5 compounds having high binding energy for multiple targets. Now what would be the next step. There are numerous docking studies available online. But after docking, none has specified what should be done? In-vitro targeting is one of the option. But I have came across very few papers for the same. Can anyone suggest me what should be done next?
Thank you for your time.
what are the binding affinities of the ligands with the SARS CoV 2 receptors? You may have to compare your docking profile with known inhibitors of the virus and discuss the similarity or the superiority of your compounds over the standard drug. Furthermore, conduct molecular dynamics to evaluate the stability of the ligand in the binding site of the receptor.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832910/
you may find the above link useful.
Best of luck
Dear Bashir, thank you for your answer. I have compared my docking scores with standard drug and found that my compounds are having comparable values. And thank you for suggesting molecular dynamics. I will go for that.
Thank You Mayur Mukhi for answer.
Dear Vijay,
Beside molecular dynamics, you may also try using in silico ADME-Tox tools to predict their pharmacological and toxicology properties. You can check this paper for more information:
Article In silico identification of 2-oxo-1,3-thiazolidine derivativ...
Thank you @Arli Aditya Parikesit sir.
I will go for that too..
And sir is it possible to go for in vitro study ?
Like we take an enzyme (spike, protease, RdRp) and test our drug against it ?
Article Development of robust in vitro RNA-dependent RNA polymerase ...
dear vijay...
If you want to continue your research to find drugs for therapy, you have to modify the structure of the chemical compounds you find. All opportunities for the chemical structure are carried out by molecular docking as an anti-Covid-19 virus. The next step is to collaborate with organic synthesis experts to conduct drug synthesis studies from chemical compounds found as anti-viral drugs. this is a very long step.
I got your point sir.
Let me share a little bit more information about my study.
The compounds I have selected for docking are already available in market in pure form. Its like drug reproposing.
More over sir.. I am planning for studies on Vero E6 cells as next step.
Still I have an query.
As per docking studies my compounds are having high affinity for multiple sites.
Now is it possible that i check the same thing in vitro..
As kits for RdRp, Protease, Spike proteins of SARS CoV 2 are available in market ...but i havent seen much research work on the same..there are very very few articles...not sufficient to decide.
Please suggest your opinion.
And once again thank you so much sir for your time.
thank you vijay.
I think currently research on covid-19 is aimed at finding a vaccine. discovery of new drugs is not yet a priority. in time drugs will be very important for Covid-19.
I support your research to continue until you get the covid-19 drug.
Thank you sir for showing such support..
Thanks for your kind words sir
Vijay Kevlani molecular docking and simulations are OK but i feel every outcome of computational data must be validated using experimental protocols. So, next can be done is Identification of particular cell line over which corona virus specifically invades with higher expression of ACE2 (human alveoli cells can be better option) and expose the cell lines to corona virus and allow to replicate it within cells. Then, since you were interested over main protease, expose the corona infected cell lines with test agent (suspected main protease inhibitors) for a specific period and quantify the the cleavages main protease which may be processed via the RT-PCR or northern blot and may be interpreted with CT value for RT-PCR and grey or integrated value of the blot (northern blot) using image processing software (I use ICY to analyze the figure).
Thank you.
Thank you Pukar sir...I have started the same. Still thanks alot for your guidance.
I totally agree with Mr. Pukar Khanal . The compounds with high fitness scores must be examined in vitro/ in vivo considering the great number of false-positives when molecular docking simulations are applied.
(please check - Awuni Y, Mu Y. Reduction of false positives in structure-based virtual screening when receptor plasticity is considered. Molecules. 2015;20(3):5152-5164. doi:10.3390/molecules20035152)