Abstract
In the present report, we describe two small molecules with broad-spectrum antiviral activity. These drugs block the formation of the nodosome. The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces the expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses, enteroviruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Another drug that inhibits receptor-interacting serine/threonine protein kinase 2 (RIPK2), which functions downstream of NOD2, also decreased the replication of these pathogenic RNA viruses. The antiviral effect of this drug was particularly potent against enteroviruses. The broad-spectrum action of nodosome-targeting drugs is mediated in part by the enhancement of the interferon response. Together, these results suggest that further preclinical investigation of nodosome inhibitors as potential broad-spectrum antivirals is warranted.
Keywords: COVID-19; NOD2; RIPK2; SARS-CoV-2; antiviral; arbovirus; broad spectrum; coxsackievirus; interferon; nodosome.
【저자키워드】 COVID-19, SARS-CoV-2, Antiviral, interferon, NOD2, RIPK2, arbovirus, broad spectrum, coxsackievirus, nodosome., 【초록키워드】 coronavirus disease, Coronavirus disease 2019, coronavirus, Antiviral, Infection, interferon, drug, antiviral activity, severe acute respiratory syndrome Coronavirus, Brain, Antiviral effect, Replication, Spread, Protein, RNA viruses, NOD2, broad-spectrum antivirals, target, small molecule, oligomerization, inhibitor, expression, interferon response, function, alphaviruses, RIPK2, arbovirus, broad spectrum, coxsackievirus, nucleotide, protein kinase, causative agent, threonine, observation, acute respiratory syndrome, Zika virus, Serine, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, pathogenic, enhancement, downstream, ZIKV, Host, broad-spectrum antiviral, Cell, shown, inhibit, promote, induce, the interferon, fetal, 【제목키워드】 Strategy, inhibition, novel, Arboviruses,