- Inhibition of the binding between the spike protein present on the surface of the virus and the ACE-2 receptor present in the membrane of the host cell. This interaction mediates the entry of the virus in the cell. 
- Because ACE 2 plays a central role in the pathogenesis of COVID-19, it is thought that it could be an efficient drug target that could either treat or prevent infection. 

ACE2 normal role:
-Critical to regulate processes such as pressure, wound healing, and inflammation. 


-It helps modulate ANGII, a protein that increases blood pressure and inflammation, increasing damage to blood vessel lining and tissue. 

COVID-19:
-In response to COVID-19, ANGII has increased inflammation and the death of alveoli cells which are critical for bringing oxygen into the body...ACE2 prevents this.

-When COVID-19 virus binds to ACE2, it inhibits its action, thus increasing the effects of ANGII
 

ACE 2 Receptor as a Pharmacological Target for Treating or Preventing COVID-19

Inhibition of the viral entry by targeting the Clathrin-mediated endocytosis of the virus.

Targeting Clathrin-mediated endocytosis of SARS-CoV-2

Inhibition of important membrane, nucleocapsid and envelope viral proteins. These are structural proteins that are crucial for the virus to propagate and infect other cells.

Targeting viral membranes

Suppressing the hyper-response of the immune system due to the SARS-CoV-2 infection.

Controlling immune system hyper-responsiveness to COVID-19

- COVID-19 shows age and sex specific severity
- Estrogen and progesterone might serve protective purpose through antiviral activity or immune-mediating mechanism

Potential Sex Hormones and Hormone Therapy for COVID-19 Patients with Cancer

As of today there are no antiviral therapies available for the treatment of COVID-19. However, there have been identified some potential druggable targets.

University of California, Davis

Smith College

University of Michigan - Ann Arbor

Currently, there is no FDA-approved, consistent treatment plan for COVID-19. Treatment depends on the severity of disease, the patient's ability to self-isolate, and the presence of other risk factors. Individuals with mild to moderate cases of COVID-19 are able to treat themselves at home without hospitalization or clinical care. If an individual is hospitalized, treatments will focus on managing the most common and severe COVID-19 complications. 

Therapeutic Treatment of COVID-19

Saxena, A. Drug targets for COVID-19 therapeutics: Ongoing global efforts. J Biosci 45, 87 (2020). https://doi-org.proxy.lib.umich.edu/10.1007/s12038-020-00067-w
https://doi-org.proxy.lib.umich.edu/10.1007/s12038-020-00067-w

Drug targets for COVID-19 therapeutics: Ongoing global efforts

1- 14 day home quarantine from the day of exposure

2- Droplet, eye, and contact precautions, where appropriate for providers

3- Return precautions

4- Supportive care: encourage eating and drinking, acetaminophen for comfort/fever

5- Many hospitals are avoiding or cautious ibuprofen due to theoretical risk, but there is no scientific evidence about a link between COVID-19 and NSAIDS (03.25.2020)

Treatment of Mild COVID-19

1. Airborne precautions for aerosolizing procedures
2. Supportive care: acetaminophen for comfort/fever
3. Respiratory support
4. ARDS treatment as needed
5. Treat comorbidities
   - Suspected sepsis: empiric antibiotics
   - Flu: oseltamivir
   - Asthma/COPD: bronchodilators MDI

Treatment of Moderate COVID-19

In addition to the milder situation treatments, it often requires hospitalization and advanced ventilatory support.

Treatment of Severe COVID-19

In addition to milder case treatments, it requires circulatory support with fluid and vasopressors if clinically appropriate.

Treatment of Critical COVID-19

- Drugs
- Antiviral Treatments
- Drug-Drug Interactions of Proposed Treatments
- Traditional Treatments
- COVID-19 Pharmacokinetics

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