LOSARTAN INHIBITS SARS-CoV-2 REPLICATION IN VITRO

Edited by, SNEHA MAVIS

A recent study published in the Journal of Pharmacy and Pharmaceutical Sciences investigates the use of Losartan to protect against the pathogenesis of COVID-19.

Local RAS dysregulation has been linked to the downregulation of angiotensin-converting enzyme 2 (ACE2). This can result in pro-inflammatory, pro-apoptotoic, and pro-thrombotic effects, as well as a cytokine stormgenerated by COVID-19. Selective AT1R antagonism by angiotensin receptor blockers (ARBs) may help to reduce COVID-19-related lung pathology, according to scientists. ARBs do so by rebalancing the Ang II/angiotensin (1-7) ratio and indirectly increasing AT2R activation produced by Ang II. C21, an AT2R antagonist, was reported to improve respiratory function in COVID-19 patients' hospitalisation and fatality rates in recent studies.

The current study looked at Losartan's potential to block the deubiquitinase and deISGlase properties of SARS-CoV-2 PLpro. Losartan was also tested for its ability to suppress viral replication in pre- and post-infected vero E6 cells. Losartan was first incubated with SARS-CoV-2 PLpro and a peptide substrate containing interferon-stimulated gene product 15 at varied doses (ISG15). The results of this experiment revealed that Losartan may interact with PLpro components capable of accomodating peptide and Ub-like substrates.

Losartan inhibited Ub-AMC cleavage at a rate of 2.3% and ISG15 cleavage at a rate of 6.9%. Losartan inhibits the synthesis of viral nuclear proteins in Vero E6 cells in a dose-dependent manner (80%).