Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Abstract

In the original publication there are few errors in Figure 1. The correct Figure 1 is provided in this correction

Inhibition of canine distemper virus replication by blocking pyrimidine nucleotide synthesis with A77 1726, the active metabolite of the anti-inflammatory drug leflunomide

“…We found that A77 1726 did not have significant antiproliferative effects when the cells were seeded in confluence and incubated for 16 h. There are several explanations: (1) in this experimental setting, the cells proliferated very slowly; (2) a small amount of uridine in the serum used for cell culture could be used for Vero cell proliferation; (3) A77 1726 does not completely shut off pyrimidine nucleotide synthesis; (4) some pyrimidine nucleotides were already present in the cells when A77 1726 was added. Consistent with our observation, Xiong et al recently reported that DHO-DH knockout does not significantly affect cell proliferation [31]. Furthermore, some tumour cell lines such as A549 cells, a cell line widely used for propagating influenza virus, almost do not express DHO-DH at all [51].…”

“…Indeed, several prior studies have shown that DHO-DH inhibitors are not able to inhibit virus replication in vivo, although they have excellent antiviral activity in vitro [47][48][49]. In contrast, a recent study demonstrated that several potent DHO-DH-specific inhibitors are effective and even more effective than oseltamivir to inhibit influenza virus replication in vivo [31]. It appears that virus type (DNA vs RNA virus) and the genomic sequence of viruses may determine whether a DHO-DH inhibitor can control virus replication in vivo.…”

“…Dunn et al reported that leflunomide functions as a DHO-DHase inhibitor to suppress RSV replication in mice [28]. Xiong et al [31] recently reported that S312, a DHO-DHase inhibitor, inhibits influenza A virus replication in vitro and prolongs the survival of influenza virus-infected mice. It would be worthwhile to investigate the therapeutic value of leflunomide, a small-molecule drug that can be manufactured at low cost for veterinary use, further in respect of CDV-infected dogs.…”

“…A77 1726 also inhibits the replication of several RNA viruses, including hepatitis E virus (HEV) [26], rotavirus [27] and respiratory syncytial virus (RSV) [28]. We and others recently reported that A77 1726 inhibits the replication of influenza A virus (IAV), porcine epidemic diarrhoea virus (PEDV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [29][30][31][32]. Because A77 1726 targets multiple intracellular factors, A77 1726 inhibits different types of viruses by different mechanisms (Fig.…”

A pharmacokinetic drug–drug interaction study between rosuvastatin and emvododstat, a potent anti‐SARS‐CoV‐2 (COVID‐19) DHODH (dihydroorotate dehydrogenase) inhibitor

“… 7 , 8 Furthermore, lethality associated with SARS‐CoV‐2 infection has been associated with excessive activation of the immune response. 8 Emvododstat has a dual mechanism of action that inhibits SARS‐CoV‐2 replication and attenuates the production of pro‐inflammatory cytokines. 2 In vitro, cell culture assays indicate a decreased capsid protein (EC 50 1.96 nM) and decreased viral titer (EC 50 2.6 nM, EC 90 53 nM) of SARS‐CoV‐2 following cell exposure to emvododstat.…”