Antiviral activity of K22 against members of the order Nidovirales

Rappe, J.; Wilde, Adriaan de; Han, Dongyi; Müller, Christin; Stalder, Hanspeter; V’kovski, Philip; Snijder, Eric J.; Brinton, Margo A.; Ziebuhr, John; Ruggli, Nicolas; Thiel, Volker

doi:10.1016/j.virusres.2018.01.002

Cited by 19 publications

(14 citation statements)

References 64 publications

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“…187 RNA synthesis inhibitors, which reduce the formation of double-membrane vesicles, a hallmark of CoV2 replication, have been identified as potential antiviral drugs. 188,189 A double-stranded RNA activated caspase oligomerizer (DRACO) that targets long viral double-stranded RNA and induces apoptosis of infected cells, but spares healthy cells, might also be useful in the treatment of CoVs. 190…”

Section: Rna Synthesis Inhibitorsmentioning

confidence: 99%

Coronavirus Infections in Children Including COVID-19

Zimmermann

Curtis

2020

Pediatric Infectious Disease Journal

924

459

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Coronaviruses (CoVs) are a large family of enveloped, singlestranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multiorgan failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

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Section: Rna Synthesis Inhibitorsmentioning

confidence: 99%

Coronavirus Infections in Children Including COVID-19

Zimmermann

Curtis

2020

Pediatric Infectious Disease Journal

924

459

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“…This should also reduce the risk of animal losses due to opportunistic infections such as fulminating pneumonia in young foals. Only a recent study, exploring the inhibition of nidoviruses by the broad-spectrum antiviral molecule K22 in infected hamster cells (BHK-21), reported the first evidence of EAV inhibition by a synthetic molecule 29 . The identification of BSA was until now impeded by the lack of suitable assay for monitoring EAV growth in high-throughput settings.…”

Section: Discussionmentioning

confidence: 99%

Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors

Valle-Casuso

Gaudaire

Martin-Faivre

et al. 2020

Sci Rep

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RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is largely insufficient to prevent new EAV outbreaks around the world. In this study, we present a high-throughput in vitro assay suitable for testing candidate antiviral molecules on equine dermal cells infected by EAV. Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. These molecules effectively suppressed cytopathic effects associated to EAV infection, and strongly inhibited viral replication and production of infectious particles. Since ribavirin is already approved in human and small animal, and that several DHODH inhibitors are in advanced clinical trials, our results open new perspectives for the management of EAV outbreaks. Viruses with a RNA genome infect both animals and plants, and dominate the eukaryotic virome by their diversity and deleterious effects 1. Indeed, RNA viral infections are a substantial public health burden affecting humans and domestic animals 2. The pandemic of SARS-CoV-2 coronavirus is the latest and most striking example with thousands of deaths reported so far in different countries in the world. Horses are not an exception, and five of seven equine viruses listed by the World Organization for Animal Health are RNA viruses (OIE). Unfortunately, the veterinary therapeutic arsenal to fight against equine viral diseases is limited, or even not-existent as no antiviral molecule is listed today. During the last years, several studies have used high-throughput screening (HTS) techniques to scan small compound libraries that could impair the replication of equine viruses. These studies were mostly focused on zoonotic viruses like West-Nile virus 3,4. Non-zoonotic equine RNA viruses, such as equine arteritis virus (EAV), were not included in those screenings. Equine arteritis virus (EAV) is a positive-sense single-stranded RNA virus, member of the subfamily Equarterivirinae, member of the family Arteriviridae, genus Alphaarterivirus from order Nidovirales like the Coronaviridae. Equine viral arteritis disease is a recurrent viral infection that causes important economic losses to the horse industry. In most of the cases, EAV infection is subclinical, but some viral strains are virulent and induce fever with body temperature going up to 41 °C, depression, anorexia, edema, nasal discharge, and conjunctivitis. EAV is a virus transmitted by respiratory or venereal routes.

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“…Following a screening which aimed at identifying anti-HCoV-229E compounds, we have described a potent small-compound inhibitor, K22, which efficiently inhibited coronavirus replication and was recently shown to additionally inhibit a wide range of virus species within the families Coronaviridae and Arteriviridae ( 12 , 13 ). K22 has been shown to act on early postentry stages of coronavirus replication and to target membrane-bound RNA synthesis by interfering with the establishment of virus-induced replicative structures.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, K22 inhibited a broad range of coronaviruses from several phylogenetic lineages (alpha-, beta-, and gammacoronaviruses), including murine hepatitis virus (MHV), type I feline coronavirus (FCoV), and avian infectious bronchitis virus (IBV), as well as the highly pathogenic human severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) ( 12 ). Furthermore, it was recently reported that K22 impairs the replication of not only viruses in the Coronavirinae subfamily but also members of the Torovirinae subfamily, such as white beam virus (WBV; genus Bafinivirus ) and equine torovirus (EToV; genus Torovirus ), as well as porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV), which are representative arteriviruses ( 13 ).…”

Section: Introductionmentioning

confidence: 99%