Angiotensin II Receptor Blockers (ARBs Antihypertensive Agents) Increase Replication of SARS-CoV-2 in Vero E6 Cells

Front Cell Infect Microbiol. 2021 Jun 11:11:639177. doi: 10.3389/fcimb.2021.639177. eCollection 2021.

Abstract

Several comorbidities, including hypertension, have been associated with an increased risk of developing severe disease during SARS-CoV-2 infection. Angiotensin II receptor blockers (ARBs) are currently some of the most widely-used drugs to control blood pressure by acting on the angiotensin II type 1 receptor (AT1R). ARBs have been reported to trigger the modulation of the angiotensin I converting enzyme 2 (ACE2), the receptor used by the virus to penetrate susceptible cells, raising concern that such treatments may promote virus capture and increase their viral load in patients receiving ARBs therapy. In this in vitro study, we reviewed the effect of ARBs on ACE2 and AT1R expression and investigated whether treatment of permissive ACE2+/AT1R+ Vero E6 cells with ARBs alters SARS-CoV-2 replication in vitro in an angiotensin II-free system. After treating the cells with the ARBs, we observed an approximate 50% relative increase in SARS-CoV-2 production in infected Vero E6 cells that correlates with the ARBs-induced up-regulation of ACE2 expression. From this data, we believe that the use of ARBs in hypertensive patients infected by SARS-CoV-2 should be carefully evaluated.

Keywords: COVID-19; SARS-CoV-2; Vero E6 cells; angiotensin I converting enzyme 2; angiotensin II receptor blockers; antihypertensive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists* / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Antihypertensive Agents / pharmacology
  • COVID-19*
  • Humans
  • Renin-Angiotensin System
  • SARS-CoV-2

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents