Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.
【저자키워드】 TMPRSS2, 【초록키워드】 COVID-19, Treatment, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, coronavirus, translation, SARS-COV-2 infection, bioinformatics, G-quadruplex, Infection, lung, severe acute respiratory syndrome Coronavirus, virus, coronavirus 2, RNA, Regulatory, Severe acute respiratory syndrome, pseudovirus, SARS-CoV-2 genome, Lungs, Factors, Mouse models, mechanism, COVID-19 patients, acute respiratory syndrome, biochemical, acute respiratory syndrome coronavirus, SARS-CoV-2 entry, effort, protein level, Host, Prevent, Cell, consequence, host molecules, identify, assays, inhibit, canonical, attenuate, 【제목키워드】 RNA, reduce,