Abstract
Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.
Keywords: Mpro; drug discovery; dyphylline; human coronaviruses (HCoVs); repurposing.
【저자키워드】 Drug discovery, repurposing., MPro, dyphylline, human coronaviruses (HCoVs), 【초록키워드】 viruses, SARS-CoV-2, Drug discovery, Antiviral, COVID-19 pandemic, Human, HCoV-OC43, repurposing, Virtual screening, protease, respiratory diseases, MPro, viral replication, humans, zoonotic, Cell culture, HCoV, Mild, Alpha, HCoV-229E, NL63, targets, antiviral agent, OC43, human coronaviruses, HCoV-NL63, dyphylline, structures, histidine, life cycle, Support, Virus life cycle, Cystine, xanthine, FDA-approved drug, severe respiratory disease, CoVs, severe respiratory diseases, catalytic dyad, HCoVs, highly pathogenic, functional enzymes, bind, human coronavirus, virus, inhibited, coronavirus, functional enzyme, therapeutically target, 【제목키워드】 antiviral therapy, dyphylline,