Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants.

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 µM, 8.5 µM, 24.1 µM, 8.2 µM and 13.6 µM, respectively. A separate experiment focusing on a combination of 10 µM stenoparib and 0.5 µM remdesivir, an antiviral drug, resulted in over 80% inhibition of the alpha variant, which is substantially greater than the effect achieved with either drug alone, suggesting at least additive effects from combining the different mechanisms of activity of stenoparib and remdesivir.

Quantitative levels of norovirus and hepatitis A virus in bivalve molluscs collected along the food chain in the Netherlands, 2013-2017.

Contamination of bivalve molluscs with viruses is well recognized as a food safety risk. A microbiological criterion for norovirus (NoV) and hepatitis A virus (HAV) in shellfish, however, does not exist in the European Union currently. The aim of this study was to evaluate the contamination levels of these viruses for fluctuation over a long period (2013-2017) in oyster (n = 266) and mussel samples (n = 490) using a method based on ISO/TS 15216-1: 2013. Samples were taken at different points in the food chain, either directly post-harvest, at Dutch dispatch centers or in retail stores, from September until March of each year. Altogether, 53.1% of the mussel and 31.6% of the oyster samples tested positive for NoV RNA. Simultaneous presence of NoV GI and GII RNA was observed in 31.6% of mussel and 10.2% of oyster samples. Contamination levels in NoV positive mussel samples collected post-harvest from B-areas were significantly higher than in those collected post-harvest from A-areas, or at dispatch centers or retail stores. Levels in oysters from dispatch were significantly lower than those collected in retail stores. Ready for sale mussels and oysters contained 2.04 and 1.76 mean log10 transformed NoV genome copies/gram (gc/g), respectively. GII levels were at a constant level in ready for sale mussels throughout all sampling periods in the study. This seemed to be true for oysters as well. HAV RNA was detected in only one of the tested mussel samples (n = 392) (typed HAV 1A) and in none of the tested oyster samples (n = 228). Critical evaluation of NoV and HAV levels in shellfish can be of help for risk assessment and risk management actions.

An international outbreak of Salmonella enterica serotype Enteritidis linked to eggs from Poland: a microbiological and epidemiological study.

BACKGROUND: Salmonella spp are a major cause of food-borne outbreaks in Europe. We investigated a large multi-country outbreak of Salmonella enterica serotype Enteritidis in the EU and European Economic Area (EEA). METHODS: A confirmed case was defined as a laboratory-confirmed infection with the outbreak strains of S Enteritidis based on whole-genome sequencing (WGS), occurring between May 1, 2015, and Oct 31, 2018. A probable case was defined as laboratory-confirmed infection with S Enteritidis with the multiple-locus variable-number tandem repeat analysis outbreak profile. Multi-country epidemiological, trace-back, trace-forward, and environmental investigations were done. We did a case-control study including confirmed and probable cases and controls randomly sampled from the population registry (frequency matched by age, sex, and postal code). Odds ratios (ORs) for exposure rates between cases and controls were calculated with unmatched univariable and multivariable logistic regression. FINDINGS: 18 EU and EEA countries reported 838 confirmed and 371 probable cases. 509 (42%) cases were reported in 2016, after which the number of cases steadily increased. The case-control study results showed that cases more often ate in food establishments than did controls (OR 3·4 [95% CI 1·6-7·3]), but no specific food item was identified. Recipe-based food trace-back investigations among cases who ate in food establishments identified eggs from Poland as the vehicle of infection in October, 2016. Phylogenetic analysis identified two strains of S Enteritidis in human cases that were subsequently identified in salmonella-positive eggs and primary production premises in Poland, confirming the source of the outbreak. After control measures were implemented, the number of cases decreased, but increased again in March, 2017, and the increase continued into 2018. INTERPRETATION: This outbreak highlights the public health value of multi-country sharing of epidemiological, trace-back, and microbiological data. The re-emergence of cases suggests that outbreak strains have continued to enter the food chain, although changes in strain population dynamics and fewer cases indicate that control measures had some effect. Routine use of WGS in salmonella surveillance and outbreak response promises to identify and stop outbreaks in the future. FUNDING: European Centre for Disease Prevention and Control; Directorate General for Health and Food Safety, European Commission; and National Public Health and Food Safety Institutes of the authors' countries (see Acknowledgments for full list).

Monitoring of pork liver and meat products on the Dutch market for the presence of HEV RNA.

The aim of the present study was to assess pork liver and meat products present on the Dutch market for the presence of hepatitis E virus (HEV) RNA. HEV RNA was detected in 27.3% of 521 products sampled from Dutch retail stores in 2016. 12.7% of livers were positive for HEV RNA (n = 79), 70.7% of liverwurst (n = 99), 68.9% of liver pate (n = 90), but in none of the pork chops (n = 98), fresh sausages (n = 103) or wild boar meat (n = 52). The highest level of HEV RNA contamination was observed in a liver (reaching up to 1 × 106 copies/g), followed by ready to eat liverwurst and liver pate (up to 3 × 104 copies/g and 7 × 104 copies/g respectively). Sequence analyses revealed mainly genotype 3c, but also some 3a, 3e and 3f strains. One strain derived from a liver sample was 100% (493 nt) identical with one isolated from a HEV case with onset of disease close in time and geography, although no direct epidemiological link could be established. Despite liverwurst and liver pate undergo heat treatment (information dd. Mid 2017) that may be sufficient to inactivate HEV, persons at risk, including Dutch transplant recipients, have been advised to avoid the consumption of raw liver as well as liverwurst and liver pate.

Porcine blood used as ingredient in meat productions may serve as a vehicle for hepatitis E virus transmission.

The aim of the present study was to investigate whether the use of porcine blood(products) in food could be a risk for a hepatitis E virus (HEV) infection. HEV RNA was detected in 33/36 batches of (non-heated) liquid products and in 7/24 spray dried powder products. Contamination levels varied among the products, but were highest in liquid whole blood, plasma and fibrinogen reaching levels of 2.2×102 to 2.8×102 HEV genome copies per 0.2g. Sequence analyses revealed genotype 3 strains, of which two were 100% (493nt) identical to recently diagnosed HEV cases, although no direct epidemiological link was established. The industry provided information on processing of blood products in (ready-to-eat)-meat. From this, it was concluded that blood products as an ingredient of processed meat may not be sufficiently heated prior to consumption, and therefore could be a vehicle for transmission.