Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro.

ABSTRACT

Angiotensin converting enzyme 2 (ACE2), an entry receptor found on the surface of host cells, is believed to be detrimental to the infectious capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Scientists have been working on finding a cure since its outbreak with limited success. In this study, we evaluated the potential of 5-aminolevulinic acid hydrochloride (ALA) in suppressing ACE2 expression of host cells. ACE2 expression and the production of intracellular porphyrins following ALA administration were carried out. We observed the reduction of ACE2 expression and intracellular porphyrins following ALA administration. ALA suppressed the ACE2 expression in host cells which might prevent binding of SARS-CoV-2 to host cells. Co-administration of ALA and sodium ferrous citrate (SFC) resulted in a further decrease in ACE2 expression and increase in intracellular heme level. This suggests that the suppression of ACE2 expression by ALA might occur through heme production. We found that the inhibition of heme oxygenase-1 (HO-1), which is involved in heme degradation, also resulted in decrease in ACE2 expression, suggesting a potential role of HO-1 in suppressing ACE2 as well. In conclusion, we speculate that ALA, together with SFC administration, might serve as a potential therapeutic approach in reducing SARS-CoV-2 infectivity through suppression of ACE2 expression.