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Strengthening CoViD-19 therapy via combinations of RAS modulators

Veselina V Uzunova1, Angel Todev2, Jacqueline Zarkos2

  • 1University of Warwick, School of Life Science, Coventry, UK.

Medical Hypotheses
|April 2, 2021
PubMed

Insights

COVID-19 pathology involves the renin-angiotensin system (RAS). Targeting this system with MAS-receptor and angiotensin-II-type-2-receptor agonists may synergistically combat viral effects and improve patient outcomes.

Area of Science:

  • Cardiovascular Research
  • Virology
  • Pharmacology

Background:

  • COVID-19 pathology is linked to the renin-angiotensin system (RAS).
  • SARS-CoV-2 infection blocks angiotensin-converting enzyme 2 (ACE2), disrupting RAS balance.
  • This disruption causes increased vascular tone, fibrosis, and immune responses.

Purpose of the Study:

  • To model the biased regulation of RAS by angiotensin II and angiotensin-(1-7).
  • To propose therapeutic strategies for compensating ACE2 loss in COVID-19.
  • To investigate the synergistic potential of combined RAS modulators.

Main Methods:

  • Utilized an unequal-arm lever model to represent RAS regulation.
  • Analyzed the impact of SARS-CoV-2 on RAS dynamics.
  • Focused on the combined application of MAS-receptor and angiotensin-II-type-2-receptor agonists.

Main Results:

  • The model illustrates how SARS-CoV-2 disrupts the balance between angiotensin II and angiotensin-(1-7).
  • A combination therapy is proposed to counteract the excess of angiotensin II and scarcity of angiotensin-(1-7).
  • This dual-agonist approach may offer synergistic anti-hypoxic, anti-fibrotic, and anti-proliferative effects.

Conclusions:

  • Combined RAS modulation offers a promising therapeutic avenue for COVID-19.
  • Simultaneous use of MAS-receptor and angiotensin-II-type-2-receptor agonists may improve clinical management of COVID-19.
  • This strategy holds potential for both acute and chronic COVID-19 complications.
Keywords:
AT2 receptor agonistsCoVid-19Combinations of modulatorsMAS receptor agonistsRenin-angiotensin system

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