A Drug to Handicap COVID-19—The Dawn of Victory?

With the massive COVID-19 epidemic, mutant viral strains have emerged, including Alpha, Beta, Gamma, Delta, and Omicron, some of which have a stronger infectious ability or immune escape ability. Meanwhile, the Omicron mutant strain was recognized as the most concerning strain worldwide currently.

Primary research has shown that SARS-CoV-2 infects human cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is the surface stinger protein and the major target of the human immune system. Thus, ACE2 is the major host entry receptor for SARS-CoV-2.

Wouldn't turning off the ACE2 receptor preclude all variants?

On December 5, 2022, researchers from the University of Cambridge published a study in the journal of Nature entitled "FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2", which showed that ursodeoxycholic acid (UDCA), a liver disease drug, can shut down ACE2 receptors and prevent viral entry, thus leading to the hypothesis of UDCA for the prevention of SARS-CoV-2 infections. Additionally, because UDCA takes action on the host cell rather than the virus, it may further prevent new viral variants as well as other coronaviruses that may emerge.

Vaccines are known to protect human bodies by strengthening the immune systems, allowing the induction of antibodies to identify and destroy pathogens, which, however, do not apply to everyone, including those with compromised immune systems. Meanwhile, viral pathogens may also mutate in order to avoid being recognized by vaccine-induced antibodies. Therefore, it is critical to identify effective strategies to curb and defend against SARS-CoV-2.

Furthermore, researchers of this work have previously used organoids to explore bile duct disorders. During the organoid study, researchers discovered the chemical FXR that is abundant in the bile duct-like organs and, more crucially, can directly regulate the opening and closing of ACE2 receptors. Researchers also discovered that UDCA, a generic medicine used to treat liver illness in primary biliary cholangitis, can suppress FXR and shut the ACE2 pathway.

Animal tests revealed that UDCAs treated hamsters were protected from the Delta strain infection. Meanwhile, researchers have also enlisted eight volunteers under UDCAs for the detection of reduced ACE2 levels, which suggested a lesser likelihood of viral infiltration and nasal infection.

The relevance of this work regards the discovery of an existing medicine that can prevent SARS-CoV-2 as well as novel variations. Because UDCA operates on human cells, it is unaffected by viral mutations and should remain effective even with new variants emerging. Furthermore, because UDCA has been approved clinically, it is considered safe and effective, and affordable tablets can be manufactured rapidly in large amounts.

It is often wise to make strategic decisions with all considerations, so diagnostic and therapeutic discovery should not be limited to only one way. Common vaccine preventions cover in silico vaccine, live attenuated and killed vaccine, recombinant subunit vaccine, and SARS-CoV-2 DNA vaccine. Therapeutic options that are under heated development track cover inhibitors, antibodies, peptides, broad-spectrum antiviral drugs, and aptamers.

A fan of biotechnology who likes to post articles in relevant fields regularly