Agonists of Toll-Like Receptors (TLRs) have been shown to broadly activate different immune populations and have had both preclinical and clinical success as adjuvants in vaccination and in the treatment of a variety of viral pathogens (218). For example, CpG oligodeoxynucleotides (CpG ODNs) are short DNA sequences that contain unmethylated CpG dinucleotides which activate TLR9 particularly on DCs and B cells (219). Bao et al. showed that their CpG ODN construct, BW001, had protective effects against SARS-CoV-1 in a mechanism that relied on NK cell activation likely through a DC intermediate (220). Amidst the ongoing SARS-CoV-2 pandemic, two clinical trials (NCT04313023, NCT04312997) have opened using the TLR2/6/9 agonist, PUL-042, in order to prevent infection.