ウイルス感染症の治療薬の素となる化合物を海洋生物から見つけたい

Objective

In 18 months of combat against COVID-19, so many researches have tried to find antiviral drugs for the disease. Now clinical trials of some of these candidates are disclosed, however; no "real remedies" have yet been found. This shows the difficult nature of antiviral drug discovery. Now vaccines for COVID-19 are being developed and we hope number of patients will decrease  considerably. However, antiviral drugs are still important because they can serve as frontline defense when no vaccine is available. Drugs can be distributed to developing countries and quickly taken by patients relative to vaccines.

 In this project, we search for naturally occurring molecules form marine organisms that inhibit infection of SARS-CoV2 and other viruses.

 

 

 

Why Marine?

Traditionary, naturally occurring molecules (we call them natural products) are widely used as medicine. The reason we look into marine life is that they are relatively under explored, albeit many interesting drug candidates have been found from the sea. In fact, many antiviral compounds are actually originated from a marine sponge-derived compound, called spongouridine. Remdesivir a compound developed as anti-Ebola virus drug is one example.

 

Marine organisms such as sponges and sea squarts are so soft and sessile that they must defend themselves from predators. They often produce chemicals for their protection.

 

 

I have been working on discovery of marine natural products with biomedical potential and found many new molecules from the sea. Among them, two compounds have actually developed as anticancer medicine by Spanish company PharmaMar. One of them trabectedin was developed and widely used to treat sarcoma.

 

 

​ ​​Yondelis is an anticancer drug from the sea squirt (tunicate)

 

Interestingly, the other compound aplidin which was also developed as anticancer drug was recently reported in Science to be effective antiviral drug for COVID-19. These examples demonstrate great potential of marine lives.

 

​ ​​ My Ph.D. Thesis. I am pointing at antiviral activity of Aplidin.

 

Why crowdfunding?

Supported by Japanese government, we have collected about 400 marine organisms last year and tested them for inhibition of SARS-CoV2 (a virus responsible for COVID-19), to cultured cells, and found 30 extract showing activity. We also tested previously isolated compounds in the same assay and found one compound completely inhibited the virus infection. However, the grant term has ended as of March 31. To continue our research, we need to find the way to raise grant in a short period of time. Crowd funding is as excellent strategy for this purpose.

 

Our plan and goal

In this project we aim to find more active extracts and isolate antiviral compounds from them to expand diversity of potential candidate drug library.  To do so will go two or more sampling expeditions and collect 400 samples by SCUBA diving. Extract samples for testing and carry out antiviral assay using real SARS-CoV2. Not many discovery researches use real SARS-CoV2 virus because it should be handled in biosafety lebel-3 laboratory (BSL-3) by specifically trained researchers. This setting is not easily accessible, but I luckily found collaborator who conduct the assay. The extract with antiviral activity will be separated and antiviral compounds will be purified. We then determine chemical structures of the compounds. 

 

​ ​​ Marine organisms we have collected. We found 30 extracts showing anti-corona virus activity out of 400 samples. 

 

Significance 

 We expect to find new antiviral compounds. This means that we will gain knowledge of what structure inhibits viral infection. This is extremely important to develop new drugs. In many cases natural products are difficult to produce in large scale. For this reason, they themselves may not be directly used as drugs. But knowledge of the key structure for antiviral activity provides us with useful starting point to design new drugs.

 

Budget

To collect 400 new marine organisms, we will have two diving expeditions in Japan. Travel expenses, boat charter, sample transportation will take 2000000-yen. For extraction, isolation and structure determination we estimate 1000000-yen for chemical reagents and instrument fees. We estimate 1000000-yen to run antiviral assay.

 

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Ryuichi Sakai, Ph.D.

Hokkaido University, School of Fisheries Sciences

Ph.D. from School of chemical science, University of Illinois at Urbana-Champaign

 

Publication on Google Scholar

https://scholar.google.com/citations?hl=ja&user=hGd2LKsAAAAJ