Yes sir, the race to find a vaccine for coronavirus is on high mode and there are efforts for turning all the stones. I hope, you may find the following paper as useful for broader perspective.

Article The race for coronavirus vaccines: a graphical guide

The race for coronavirus vaccines: a graphical guide

Traditional vaccine techniques do not necessarily need "improvement". Already they have protected multiple billions of humans, leading to the eradication of major viral diseases. This track record seems to give us a pretty good shot at COVID with traditional approaches. Why not take advantage of what we've got?

When you're trying to innovate too much, you can have the opposite problem -- you don't know if all that innovation will work as well as the traditional approaches. (Gene Vaccines, I'm talking to you, but by no means only to you...)

Thanks Sandeep Kumar Dhanda for providing excellent link. There are number of issues with traditional approach that include cyto/hemo toxicity and allergenicity.

Dear Prof. Raghava!

YOU pointed to an essential point. Despite massive investments and efforts, vaccine might not be available in the time-frame required: within a year. In my view here there is a need for gene-transfer technology based solutions:

1) Charles Schmidt (2020). "Genetic Engineering Could Make a COVID-19 Vaccine in Months Rather Than Years - Candidates are speeding toward human trials " April 29, 2020, © 2020 SCIENTIFIC AMERICAN, A DIVISION OF SPRINGER NATURE AMERICA, INC. Available at:

https://www.scientificamerican.com/article/genetic-engineering-could-make-a-covid-19-vaccine-in-months-rather-than-years1/

2) Muhammad Adnan Shereen et al. (2020). "COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses" Journal of Advanced Research, Volume 24 July 2020, Available at:

Article COVID-19 infection: Origin, transmission, and characteristic...

Yours sincerely, Bulcsu Szekely

Agree with Sandeep Kumar Dhanda

Most importantly, the virus does not limit us in scientific research.

But, it is our priority to think of the future as well. Now, at present, the entire world is suffering from this disaster, and there are billions of people placing demands on this vaccine. Then in that situation, it would be nearly impossible to make so many traditional vaccines so as to reach out to these billions of people by taking a maximum of about one-two months time given that their design takes a lot of time. Above all, they would be very effective, but by the time they would be designed in numbers, there would be so many deaths, which is also not desirable.

Development of peptide vaccines, a computer-assisted method to design vaccines in much lesser time and much lesser cost is a very good alternative in this case.

The following is the link for our work that is currently going on regarding the peptide vaccine design for CoVID 19:

https://sciforum.net/paper/view/conference/6787

A traditional or modern approach, it is important to be effective.

The Rise of New Coronavirus Infection (COVID-19): A Recent Update

• DOI: 10.14744/ejmo.2020.22222

The true vaccine for Covid 19 might be lying in the hands of traditional medicine if they can be given a chance

Subhamoy Biswas Thanks for sharing your peptide-based concept. Time delay in vaccine is not due to synthesising protein or peptide, major time consuming step is clinical trial. Even if your vaccine candidate is perfect, it will take year to get clearance after clinical trial. My major concern is why all are using traiditional approach not peptide-based vaccine, in case of peptide-based vaccine size is optimized and toxicity is minimized.

Bulcsu Szekely Thanks for sharing excellent work, these approach are used in vaccines undertrial. Clinical trials on human is major challenge, it take its own time.

Actually, the most important vaccines for human diseases were developed via traditional methods...

We should develop vaccines by all possible approaches and evaluted at the same time, time issue is what we need, I think the world would not concern about the approach even a live attenuated vaccine works well.

The efficacy of vaccine is desperately needed regardless the approach of manufacture.

Finally, i urge all scientists to develop vaccines with any possible approaches

Dear Dr. have a nice Sunday.

In my RG open question about the dramatic situation of Lombardia (N.Italy)

I propose the test of the natural compounds from Artemisia, according to previous extensive bibliographical reviews about toxic effect in potential biocontrol.

I hope this is useful.

RG open question and Artemisia review references: https://www.researchgate.net/post/The_novel_Coronavirus_in_N_Italy_Lombardia_COVID19_2019nCoV_SARSCoV2_shows_a_fatality_rate_compatible_with_SARS-MERS_Why#view=5eabf2ae32592944281a872b

______________________________________

https://www.researchgate.net/figure/ResGa-FxFac-post_fig102_339781431

|n.2|....The following 12 virus species have been recognized, both DNA-virus and RNAvirus, both phyto-virus and zoo-virus: BVDV bovine viral diarrhea virus; COPV, canine papilloma virus; DEN/2, dengue virus 1; FIV, feline immunodeficiency virus; HBV, human hepatitis B virus; HCMV, human cito-megalo virus; HFLUV, human influentia virus; HIV, human immunodeficiency virus; HSV/1, human herpes virus 1; HSV/2, human herpes virus 2; JUNV, junin virus; TMV, tobacco mosaic virus. ....

.. ... FROM Artemisia: absinthium, afra, annua, anomala, arborescens, capillaris, caruifolia, douglassiana, herbaalba,verlotorum, vulgaris.....

.. ... Natural compounds: aesculetina, arcapillina, artemisinina, artesunate, beta-arteannuina, beta-sitosterolo, deidro-artemisinina, deossi-artemisinina, isorhamnetina, N-N-N-3p-coumaroil-spermidina, stigmasterolo.

Thanks for mentioning in silico epitopes predictions. I agree that these methods, I was working on 10 years ago, are interesting to isolate T helper and T cytotoxic epitopes from genetically, stable part of viral proteins. As a vet I have experienced clinical cases of highly pathogenic coronavirus in cats (Feline Infectious Peritonitis) known since 1963. I don't think B epitopes and antibodies are long term solutions, spike protein may act as a decoy. Moreover in silico predictions are not not so easy. An epitope is immunogenic or not depending on the cytokine context, which is influenced by other vaccine components.

Hope this will be helpful https://www.natureasia.com/en/nindia/article/10.1038/nindia.2020.81

The COVID-19 vaccine development landscape..

https://www.nature.com/articles/d41573-020-00073-5

Gajendra Pal Singh Raghava -----------Prof. GPS.R.-------Thanks for the question

It’s a million-dollar question. I am excited about your computational resources. You are great.

My concern about the question, you have validated your tools but not products (peptide vaccines). If you have had validated your products too then, make use of the tool could be more meaningful (I think----I am sorry----it is like---when preparing the rice flour (tools) cook dosa (peptides) and make sure the taste to attract the customer (practical utility)

I was refused many times using computational tools without experiment. I have used your INF prediction tools and working great.

Recently, we developed two peptide vaccine candidates which were synthesized and purified. But, still, we are waiting to conduct experimental studies for COVID. COVID experiments need adequate lab facilities.

You are well-known that most of the journals are not considering the peptides or vaccine developed from a single tool, the reviewers and experts advised using two or more tools to confirm that prediction. But, I think there is no similar kind of tool with exact matching peptides because the algorithms are different. It can give a different product length (9mer or 14mer).

Here I do feel, if the predictions of is not acceptable by using a single tool then, how it could be acceptable with two or more tools? Whether experts/reviewers validating the tools or authors? (Bioinformatician spending man-power, machines, money and still hanging to prove/validate their result-------without experiment)

These things are not happening to the experimentalist, they can use a single method, get results, and published (They are spending money and man-power----------They don’t need to validate again computationally).

So, the computer algorithm not equal to experimental assays-------- when the computer algorithms became accepted without experiments, then the computer (your and others) tools will be accepted as experimental results-----I hope.

I may conclude that computers need experimental dataset but Experiments do not need computer predictions partially or fully. So, experts prefer traditional vaccine development methods---I think

Gurudeeban Selvaraj Thanks for writing detail email, this is unfortunate but fact that two communities (experimental and theoretical) do not trust and respect each other work. It is nearly impossible for a single person to do both type of jobs. In the past number of group tested peptides predicted from bioinformatics tools, and most of the case they work very well.

We also discover highly potential cell penetrating with the help of bioinformatics tools in short span that shows importance of bioinformatics tools see following papers

Article Identification and Characterization of Novel Protein Derived...

Article Cell-Penetrating Peptide and Antibiotic Combination Therapy:...

Article Topical Delivery of Protein and Peptide Using Novel Cell Pen...

In addition we have many patent on this topic, overall conclusion is that both communities should work together for fast discovery.

Here, we are sharing our opinion on Covid19 vaccines under trail. Our aim is not to spread any negativity against vaccine under development, we just wish to highlight challenges these vaccine may face. Advise given in this article may help developers to overcome limitations of traditional vaccines. See url https://www.frontiersin.org/articles/10.3389/fimmu.2020.561851/full/

We are please to announce a server IL6pred for predicting interleukin 6 (IL6) inducing peptides. IL6 is a major cytokine induced by coronavirus, which is responsible for tissue damage resulting in multi-organ failure and death. Our server will help to develop safe vaccines. https://academic.oup.com/bib/advance-article-abstract/doi/10.1093/bib/bbaa259/5919792

Prof. Gajendra Pal Singh Raghava

Thanks for your kind answer and papers. Yes, I have checked your tools and databases; it is great and there are no objections. I really appreciate and salute your contributions to science.

However, I would be happier, while a legendary scientific personality like you should take forward the importance of computer-aided vaccine design with solid experimental validation results to support a young mind like me. I think you can find an experimentalist easier than budding researchers.

Because, as you well know the sound from the Tower (you) reach the destination faster than the surface (me). I wish your research papers should be converted into products for a living.

M. M. Ranjbar

Thanks for your comments. I would like to know if you get involved in any experimental studies after your immunoinformatics analysis? If yes, share your experience. If no, then you are criticizing science and insulting academicians. Because everywhere there are obstacles, if we come over we can view success or else get experience to view success. We try to fix the problem don’t discourage ideas.

Dear Dr. Ganjendra Pal Singh Raghava,

I completely agree with your question. It is sad to know that we are still following the same age-old traditional method to design vaccines in spite of so many modern and advanced techniques already been discussed and experimentally proven. Designing vaccines for an entire global population is a cumbersome task. Agreed. But, we also need to check its efficacy and safety which cannot be proved through clinical phase trials I, II and III. The long term side effects can be best depicted through T- and B-cell epitope mapping.

Thank you so much Sir, for the wonderful bioinformatics tools.

https://pubmed.ncbi.nlm.nih.gov/33136473/

Peptide vaccines are a good alternative to traditional ones for SARS-CoV-2 and they can be produced in wet labs at a much faster rate. Sir, you can have a look at this article below for a possible way to design them:

Article New Computational Approach for Peptide Vaccine Design Agains...

Subhamoy Biswas Thanks for sharing excellent paper, challenge is to bring vaccine in real life COVAXIN, COVISHIELD, Modena etc.