# COVID19: SARS-CoV-2 and ACE2 interaction in hypertension

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2021 · —

## Abstract

The current COVID-19 pandemic is one of the most disruptive events in human history, caused by the SARS-
CoV-2 virus, member of the coronavirus family that uses angiotensin converting enzyme 2 (ACE2), a
transmembrane carboxypeptidase identified as a member of the renin-angiotensin system (RAS) as an entry
point to the cells. Clinical reports suggest that pre-existing conditions such as hypertension, diabetes and obesity
predispose to COVID-19 mortality. Considering that these co-morbidities are highly prevalent in Veterans and
active duty personnel, these populations are at high risk of infection by SARS-CoV-2. The role of the brain RAS
in the maintenance of normal blood pressure (BP) and in the neuro-cardiovascular dysregulation leading to
hypertension has been firmly established. In addition, anosmia (loss of smell) is an early symptom of COVID-19
suggesting the brain is a primary target for SARS-CoV-2 infection. For the treatment of hypertension, two of the
most popular drug choices are ACE inhibitors (ACEI) and angiotensin-II (Ang-II) type 1 receptor (AT1R) blockers
(ARB). None of these classes of drugs have a direct effect on ACE2 activity, but there is evidence indicating that
they may alter long-term ACE2 expression levels and subcellular localization, suggesting that patients taking
these medications may be subject to more severe infections with SARS-CoV-2. Thus, clear data on the
relationship between ACE2 plasma membrane levels, SARS-CoV-2 and co-expression of other RAS members
are required to promptly adapt the therapy in this subset of patients. Beyond establishing ACE2 as a critical
player in the prevention of neurogenic hypertension, our group was the first to report that Ang-II mediates ACE2
internalization and degradation via AT1R activation. Thus, the hypothesis of this proposal is that ACE2-AT1R
complexes enhance SARS-CoV-2 infection in hypertensive Veterans while RAS blockers prevent ACE2
internalization and coronavirus infection. Taking advantage of unique resources, including a humanized
transgenic mouse expressing human ACE2 constitutively, we will determine whether AT1R contribute to SARS-
CoV-2 infection and whether ACEI and ARB reduce the incidence of COVID-19.

## Key facts

- **NIH application ID:** 10152313
- **Project number:** 1I01BX005475-01
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** Eric D Lazartigues
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152313

## Citation

> US National Institutes of Health, RePORTER application 10152313, COVID19: SARS-CoV-2 and ACE2 interaction in hypertension (1I01BX005475-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10152313. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*