Scientists at QIMR Berghofer Medical Research Institute in Queensland have developed two new drugs to both prevent infection with SARS-CoV-2 and treat people who have been exposed to the virus so that they do not develop serious illness.
The peptide-based drugs are currently being tested on hamsters at the French preclinical and clinical research center, IDMIT, with promising results showing that they are non-toxic and have few side effects. The drugs are also stable and can be stored at room temperature, which would make them easy to dispense.
The results of the study were published overnight in the prestigious journal Discovery of the cells of nature.
Both early intervention drugs target how human cells respond to the SARS-CoV-2 virus, instead of the virus itself.
The first peptide drug would be given before exposure to the virus and help increase the effectiveness of vaccines, while the second drug would stop the spread of the virus in already infected cells.
The discovery of the peptide-based drugs was made possible after researchers discovered a previously unknown mode of entry that SARS-CoV-2 exploits to invade cells and cause COVID-19 disease.
Laboratory tests show that the first peptide drug reduces infection by masking the ACE2 receptor protein on human cells. The SARS-CoV-2 spike protein uses the ACE2 receptor to bind and invade cells.
The virus then clings to the camouflage peptides, which they mistake for human cells, preventing infection.
Laboratory tests have also shown that if the virus enters cells, the second peptide drug can block the way the virus hijacks the host cell and replicates. It also strengthens the ability of the immune system to recognize the virus.
Professor Sudha Rao, principal investigator and head of QIMR Berghofer’s gene regulation and translational medicine group, said he was able to develop the drugs after finding that some people had a chemical label that acts like a lock on the receptor. ACE2.
“The beacon can keep the receptor locked or open, in order to control the infection. This means that people who wear the “padlock-shaped” tag on their ACE2 receptors will be less susceptible to SARS-CoV-2 and those who are not are more vulnerable to infection, “said Professor Rao.
“Our drugs prevent removal of the label and also protect unlabeled ACE2 receptors from infection. “
The researchers also found that if the virus invaded cells, it would unlock the tag from the inside, which would allow the virus to replicate more efficiently.
“Our new peptide-based drugs can keep the lock closed and prevent infection from setting in,” Professor Rao said.
“These are the first drugs we are aware of that can work on two fronts. We hope, if the clinical trials are successful, that the first drug could be given as a treatment alongside vaccination to prevent the virus from binding to cells and taking hold, while the second peptide could be used. to stop the virus from replicating in already infected patients. “
The research was conducted on the blood of COVID-19 patients and human cells.
Professor Nabila Seddiki, who is testing the drugs at IDMIT in France, said the development of new drugs was an exciting step in the fight against COVID-19.
“Many of the drugs developed around the world to treat COVID-19 are intended for people with serious illnesses. However, these peptide-based drugs are primarily aimed at preventing infection and reducing the severity of the disease that precedes it. is really taking root, ”said Professor Seddiki.
“These drugs could also be very important because they can provide the protection we need for emerging variants and be used to protect the small group of people who cannot be vaccinated. “
Prof Rao said the collaboration with IDMIT was vital for the advancement of the study.
“IDMIT is the world leader in clinical trials and, in particular, the testing of potential drugs against COVID-19. They have access to the latest emerging strains of the SARS-CoV-2 virus, ensuring that our potential drugs are tested on the relevant strains of the virus. virus, ”Professor Rao said.
“We are very grateful to Professor Seddiki and his team for their expertise and resources to conduct the preclinical trials, and we hope these trials will progress well. “
Queensland Minister of Health Yvette D’Ath said the state government was proud to have helped fund Professor Rao’s research.
“A little over a year ago, we knew very little about this disease and it is amazing that researchers in Queensland were able to develop these potential new drugs in such a short time,” said Ms D’Ath.
“All the people of Queensland can be proud of the hard work and commitment of Professor Rao and his team in finding new weapons against this pandemic disease which continues to destroy lives around the world. ”
Wen Juan Tu et al, Targeting New LSD1-Dependent ACE2 Demethylation Domains Inhibits SARS-CoV-2 Replication, Cellular discovery (2021). DOI: 10.1038 / s41421-021-00279-w
Fourni par QIMR Berghofer Medical Research Institute
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