Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection

[Image: see text] The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease (COVID-19) is ongoing. Therefore, effective prevention of virus infection is required. Pyrroloquinoline quinone (PQQ), a natural compound found in various foods and human breast milk, plays a role in various physiological processes and is associated with health benefits. In this study, we aimed to determine the effects of PQQ on preventing coronavirus infections using a proxy Feline Infectious Peritonitis Virus (FIPV; belongs to the coronavirus family). In plaque reduction assays, we showed that pre- and post-PQQ-treated viruses were less infectious. IC(50) was 87.9 and 5.1 μM for pre- and post-PQQ-treated viral infections, respectively. These results suggest that PQQ decreased the virion stability and viral replication. RT-qPCR confirmed these results. TEM findings showed that PQQ damaged viral capsids and aggregated viral particles, leading to inhibited virus attachment and entry into the host cells. PQQ was optimized by the addition of ascorbic acid and glutamic acid, which increased the number of redox cycles of PQQ and increased reactive oxygen species production by 14 times. In vitro, PQQ inhibited 3 CL(pro)/M(pro) enzymes (an enzyme critical for viral replication) activity of SARS-CoV-2. Our results demonstrate the antiviral effect of PQQ on coronavirus, mainly by disrupting virion stability and loss of infectivity (occurring outside the host cell), due to increased redox activity. Furthermore, PQQ may hinder viral replication (inside the host cell) by 3 CL(pro)/M(pro) enzyme inhibition. In summary, this study demonstrates the antiviral effect of PQQ and its potential application in coronavirus diseases.