Drug to block COVID-19 infections in engineered human tissues

An international team has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts. The findings, published in Cell, hold promise as a treatment capable of stopping early infection of the novel coronavirus.

The study provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19, and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys.

The global health crisis of novel coronavirus pandemic is probably the greatest challenge since the World War II. The pandemic has affected most of the countries, areas or territories. The causative agent for this disease is Severe Acute Respiratory Syndrome-Related Coronavirus- 2 strain (SARS-CoV-2). Researchers all over the world are making huge efforts to develop treatment or vaccine against this novel coronavirus strain. Till date, there is no proper treatment for this COVID-19 pandemic. The only treatments in use are supportive and preventive. Thus, having a strong immune system is what helps a person to get rid of this disease and to survive.

Another fact that griped the attention of researchers is that the impact of the disease is different in different regions or countries. The difference can be because of differences in cultural norms, controlling efforts, and health infrastructure.

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ACE2 -- a protein on the surface of the cell membrane -- is now at centre-stage in this outbreak as the key receptor for the spike glycoprotein of SARS-CoV-2. In earlier work, the authors first identified ACE2, and found that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003. The laboratory also went on to link the protein to both cardiovascular disease and lung failure.

While the COVID-19 outbreak continues to spread around the globe, the absence of a clinically proven antiviral therapy or a treatment specifically targeting the critical SARS-CoV-2 receptor ACE2 on a molecular level has meant an empty arsenal for health care providers struggling to treat severe cases of COVID-19.

"Our new study provides very much needed direct evidence that a drug -- called APN01 (human recombinant soluble angiotensin-converting enzyme 2 - hrsACE2) -- soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19," says another author.

In cell cultures analyzed in the current study, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000. In engineered replicas of human blood vessel and kidneys -- organoids grown from human stem cells -- the researchers demonstrated that the virus can directly infect and duplicate itself in these tissues. This provides important information on the development of the disease and the fact that severe cases of COVID-19 present with multi-organ failure and evidence of cardiovascular damage. Clinical grade hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues.

"Using organoids allows us to test in a very agile way treatments that are already being used for other diseases, or that are close to being validated. In these moments in which time is short, human organoids save the time that we would spend to test a new drug in the human setting," says another author.

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