Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused
the current coronavirus disease 2019 (COVID-19) pandemic. Despite a preferential respiratory
tropism of SARS-CoV-2, multi-organ involvement has been described. SARS-CoV-2 entry
into host cells is mediated by the entry factors angiotensin converting enzyme 2 (ACE2)
and transmembrane serine protease 2 (TMPRSS2). Recent studies suggest that SARS-CoV-2
causes direct hepatic impairment in COVID-19 patients. Interestingly, ACE2 and TMPRSS2
are also expressed in primary human hepatocytes (PHH). Despite this evidence, data
on infection and factors modulating functional regulation of SARS-CoV-2 infection
in PHHs are scarce. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have
been described to modulate various cellular processes and have been implicated as
potential therapeutic target. We aimed to study the infection of PHHs with SARS-CoV-2
and to evaluate the potential of miRNAs for modulating viral infection. We could demonstrate
that PHHs can be readily infected with SARS-CoV-2. Bioinformatics analyses revealed
miR-200c-3p, miR-429, let-7c-5p and miR-141-3p as candidate miRNAs targeting ACE2
and TMPRSS2. All miRNAs were able to reduce SARS-CoV-2 burden in PHH by supressing
ACE2 and TMPRSS2. Our findings provide the first evidence of the applicability of
miRNA molecules in reducing SARS-CoV-2 viral loads.
