What is the role of pyronaridine tetraphosphate in treating infections caused by highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV-1, and MERS-CoV?
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Topic
Pyronaridine tetraphosphate is an antimalarial drug that has been repurposed for its antiviral and anti-inflammatory properties. It has been identified as a potential inhibitor of the papain-like protease (PLpro) of SARS-CoV-2, which is essential for viral replication. Pyronaridine has shown efficacy in vitro and in vivo against SARS-CoV-2, reducing viral load, lung pathology, and pro-inflammatory cytokine levels. Additionally, it has demonstrated broad-spectrum activity against other coronaviruses, including SARS-CoV-1 and MERS-CoV, due to the conserved nature of the PLpro domain across these viruses.
Answer
Pyronaridine tetraphosphate acts as a potent antiviral and anti-inflammatory agent against highly pathogenic coronaviruses. It inhibits the viral PLpro, reducing viral replication and lung pathology. In mouse models, pyronaridine significantly lowered viral titers, reduced lung inflammation, and improved survival rates. It also showed additive effects when combined with other antivirals like molnupiravir and nirmatrelvir, further reducing viral loads and inflammatory markers. These findings suggest that pyronaridine could be a valuable therapeutic option for treating COVID-19 and other coronavirus infections, either as a standalone treatment or in combination with existing antivirals.
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