Developing broad-spectrum antiviral compounds is important in tackling emerging viruses. Researchers at the University of Alberta, Canada have described two novel molecules with broad antiviral properties that are effective against a range of virus types, including SARS-CoV-2. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a protein receptor that recognizes the peptidoglycan muramyl dipeptide (MDP) found in certain bacteria and RNA viruses. In response to detecting MDP, NOD2 launches an immune response. In previous studies, the expression of this immune response referred to as the nodosome promoted the replication of the Zika virus in human fetal brain cells.
Zika virus belongs to the genus flavivirus, closely related to dengue fever, yellow fever, and other human pathogens. Developing an antiviral compound to suppress this response, therefore, may work to also slow or stop the replication of flaviviruses, and indeed other viruses of neighboring genera. Using multiple human cell types and cell lines two novel broad-spectrum antiviral NOD2 blocking drugs that inhibit the replication of a range of viruses: GSK717 and GSK583 were identified.
GSK717 inhibited replication of flaviviruses (the family that includes Zika and dengue), alphaviruses, enteroviruses, and SARS-CoV-2. GSK583 is a RIPK2 blocking agent (a critical mediator of NOD2 signaling) that potentially inhibits all these too, but was shown to be particularly effective against enteroviruses, the group that includes the common cold, polio, and hand-foot-and-mouth disease.
This type of broad-spectrum effectiveness is highly promising in the development of antiviral drug therapies, as these compounds may be used to prevent the replication of both recurring and emerging viruses.
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