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Find new drugs for COVID-19 using induced pluripotent stem cells





Compound screening using SeV and iPSC. (A) Construction of SeV. SeV, which carries the EGFP gene to the 3’region of viral genomic RNA, was constructed after removal of the F gene. (B) Timeline for compound screening. (C) Compound screening schema. (D and E) Results of initial screening. About 500 compounds were evaluated. The blue dot indicates negative control (DMSO). Red dots indicate the hit drugs raloxifene, rifampicin, pranlukast, zileuton, and pioglitazone. (F) List of hit compounds. The score reflects the number of EGFP-positive cells. credit: FEBS open bio (2021). DOI: 10.1002 / 2211-5463.13153

Last year, intensive research on SARS-CoV-2, the virus responsible for the COVID-19 pandemic, was seen around the world. Despite the availability of several vaccines, rapid mutations in the virus raise concerns that the infection will continue to spread. A new study led by Professor Haruhisa Inoue of CiRA shows that induced pluripotent stem (iPS) cells help find effective drugs for RNA viruses.

The HIV, Ebola virus, and current SARS-CoV-2 pandemics have caused RNA viruses to be the cause of many of society’s greatest health hazards in the last half century. One of the major challenges in managing these viruses is the high mutation rate. In fact, if SARS-Cov-2 continues to mutate, like influenza, new vaccines may be needed each year.

Inoue et al. Proposed Possible solutions use different types of RNA viruses and cells.

“A common therapeutic approach to RNA viruses like penicillin for bacterial infectious diseases is needed to treat not only current RNA viruses, but also emerging viruses,” Inoue said. “Drugs that are effective in various combinations of RNA virus and cells may have potential for the treatment of future RNA virus infections. Screen for approved drugs that prevent Sendai virus infection in iPS cells and select them. We tested whether it could be used to prevent Ebola virus and SARS-CoV-2 infection in different types of cells. “

Where Drug repositioning screens for drugs that are already known to be safe, including screening for thousands of chemicals with little known about their effects on humans. This approach has the potential to find candidate drugs faster than drug discovery.

Sendai virus is an RNA virus commonly used in iPS cell research and, unlike Ebola virus and SARS-CoV-2, does not require a high level of biosafety laboratories for testing.

From a screen of 500 drugs, five drugs, including the breast cancer and osteoporosis drugs raloxifene and pioglitazone, have shown potential for further investigation. Because of diabetes.

Although iPS cells are susceptible to Sendai virus infection, they lack important receptors that prevent SARS-CoV-2 infection.

“Studies show that SARS-CoV-2 infects cells by binding to ACE2. [angiotensin-converting enzyme 2].. SARS-CoV-2 target cells express this receptor at high levels, while iPS cells express low levels, “explains Inoue.

Therefore, to investigate these agents in Ebola virus and SARS-CoV-2 infection, this study switched iPS cells to other human and monkey cells. Consistent with its effects on Sendai virus, raloxifene was found to have antiviral activity against Ebola virus and SARS-CoV-2.

Raloxifene is a selective estrogen receptor modulator (SERM), a group of commonly used drugs for treatment. Postmenopausal symptoms such as menopause. Therefore, scientists investigated other SERMS and found three that had a suppressive effect on Ebola virus and SARS-CoV-2 infection.

On the other hand, pioglitazone was mildly effective in preventing SARS-CoV-2 infection, but not in Ebola virus infection. However, the combination of the two drugs had a slight synergistic effect on SARS-CoV-2 infection.

“These drugs, which have different effects on RNA viruses and cells, may have potential therapeutic potential for RNA. Infectious diseases, including newly emerging and mutated viruses. ”

New drug candidate for COVID-19

For more information:
Keiko Imamura et al. IPSC screening for drug diversion identifies anti-RNA virus agents that regulate host cell susceptibility. FEBS open bio (2021). DOI: 10.1002 / 2211-5463.13153

Provided by
Kyoto University

Quote: COVID-19 obtained on April 8, 2021 from https: // using induced pluripotent stem cells ( Search for new drugs (2021, April 8). html

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