Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Comparative Removal of Poliovirus, Rotavirus SA11 and MS2 Coliphage by Point-of-Use Devices used to Treat Drinking Water and Water Disinfectants: A Review.

Test protocols have been developed to test water treatment devices/systems for use for treating drinking water that are used at the individual and home level to ensure the removal of waterborne viruses. Current test procedures call for the use of poliovirus type 1 and/or rotavirus SA11. Recently we suggested that selected coliphages could be used as surrogates for poliovirus for testing of point-of-use (POU) water treatment devices, however, rotavirus was not used in those studies. The purpose of this review was to compare studies of POU devices which were tested with poliovirus type 1, simian rotavirus SA11 and coliphage MS2 to determine if the behavior of rotavirus SA11 was significantly different. In addition, an attempt was made to compare the relative resistance of these viruses by various disinfectants used to treat drinking water. In all cases SA11 was removed to an equal or greater degree than poliovirus. SA11 was found to be less resistant to halogens, although one study found it to be more resistance to chloramines than poliovirus and MS2. Based on this review, use of coliphages for testing POU devices appear justified. Additionally, data on chloramines for these viruses would be useful to determine if rotavirus is more resistant than poliovirus and MS2.

The UV Dose Used for Disinfection of Drinking Water in Sweden Inadequately Inactivates Enteric Virus with Double-Stranded Genomes.

Irradiation with ultraviolet light (UV) at 254 nm is effective in inactivating a wide range of human pathogens. In Sweden, a UV dose of 400 J/m2 is often used for the treatment of drinking water. To investigate its effect on virus inactivation, enteric viruses with different genomic organizations were irradiated with three UV doses (400, 600, and 1000 J/m2), after which their viability on cell cultures was examined. Adenovirus type 2 (double-stranded DNA), simian rotavirus 11 (double-stranded RNA), and echovirus 30 (single-stranded RNA) were suspended in tap water and pumped into a laboratory-scale Aquada 1 UV reactor. Echovirus 30 was reduced by 3.6-log10 by a UV dose of 400 J/m2. Simian rotavirus 11 and adenovirus type 2 were more UV resistant with only 1-log10 reduction at 400 J/m2 and needed 600 J/m2 for 2.9-log10 and 3.1-log10 reductions, respectively. There was no significant increase in the reduction of viral viability at higher UV doses, which may indicate the presence of UV-resistant viruses. These results show that higher UV doses than those usually used in Swedish drinking water treatment plants should be considered in combination with other barriers to disinfect the water when there is a risk of fecal contamination of the water.

At Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence of Reassortment and Zoonotic Transmissions.

Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses.IMPORTANCE The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents sheds light on the vast genetic diversity of rotaviruses and also hints at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.

Shenling Baizhu Powder Inhibits RV-SA11-Induced Inflammation and Rotavirus Enteritis via TLR4/MyD88/NF-κB Signaling Pathway.

Rotavirus enteritis (RVE) is a common acute intestinal infectious disease caused by rotavirus infection. It is an important cause of death in children younger than 5 years worldwide. Shenling baizhu powder (SBP), a classic traditional Chinese formulation, is one of the most popularly prescribed medicines for digestive diseases. Clinical studies have revealed the protective effects of SBP on RVE. However, the potential mechanism is still unclear. In this study, we aimed to evaluate the anti-rotavirus effect of SBP and its mechanism, focusing on the TLR4/MyD88/NF-κB signaling pathway. Our results demonstrated that, based on the inhibition of the virus-induced cytopathic effect in Caco-2 cells, the concentration for 50% of maximal effect (EC50) and selectivity index (SI) of SBP for RV-SA11 in the serum were 5.911% and 11.63, respectively. A total of 219 active compounds with oral bioavailability ≥30% and drug-likeness ≥ 0.18 were selected from the 10 ingredients present in the formulation of SBP, which acted on 471 potential targets. A total of 226 target genes of RVE were obtained from the GeneCards database. The protein-protein interaction (PPI) network showed that there was a close interaction between 44 common targets of SBP and RVE. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SBP acted on RVE through various inflammatory pathways and the intestinal immune network. Subsequently, we investigated the effect of SBP on TLR4/MyD88/NF-κB signaling pathway in vitro. After infection with RV- SA11, the expression of TLR4, MyD88, and NF-κB mRNA and protein increased significantly, which could be abolished by SBP treatment. In addition, the IL-1ß, TNF-α, IL-6, and IFN-ß levels increased markedly in Caco-2 cells infected with RV-SV11. Treatment with SBP partly reversed the changes of IL-1ß, TNF-α, and IL-6, while further increased the level of IFN-ß. In conclusion, our study revealed that SBP can significantly inhibit rotavirus replication and proliferation in vitro. The antiviral effect may be related to the regulation of the TLR4/MyD88/NF-κB signaling pathway, followed by the down regulation of inflammatory cytokines and up regulation of IFN-ß induced by rotavirus.

Thermal Inactivation of Hepatitis A Virus, Noroviruses, and Simian Rotavirus in Cows' Milk.

Consumption of raw or unpasteurized milk is a risk for the consumers because indirect contaminations such as fecal-cross-contamination could occur and determine the presence of enteric viruses. In this study, milk was treated with several temperature and time combinations chosen by performing a preliminary experiment to evaluate the intervals needed to inactivate Hepatitis A virus (HAV) HM175 strain, noroviruses genogroups I and II (GI and GII), and simian rotavirus SA11 at different temperatures. Results were obtained by measuring the genome copies and infectious units by real-time PCR and plaque assays respectively. At 85 °C, one minute and two minutes were needed to achieve 6.6 log10 ± 0.2 and 8 log10 ± 0 reductions of genome copies of HAV respectively. Similar genome copies reduction was also observed for noroviruses (GI and GII) and simian rotavirus. At higher temperatures, 90 s (s) at 90 °C and 60 s at 95 °C were needed to achieve 8 log10 ± 0 reductions of the genome copies of all studied viruses. Significant higher sensitivity of the infectious units of both HAV and simian rotavirus to heat treatment of milk than their genome copies was observed. At boiling point of milk (100.5 °C), 40 s were needed to achieve 8 log10 ± 0 reductions of genome copies of all the studied viruses, while 10 s were needed to achieve 6 log10 ± 0 reductions of the infectious units of HAV and simian rotavirus. Significant higher reduction of infectious units than genome copies was observed confirming that genome copies reduction does not correspond to infectious virus.

Generation of Simian Rotavirus Reassortants with VP4- and VP7-Encoding Genome Segments from Human Strains Circulating in Africa Using Reverse Genetics.

Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The broad use of two vaccines, which are based on RVA strains from Europe and North America, significantly reduced rotavirus disease burden worldwide. However, a lower vaccine effectiveness is recorded in some regions of the world, such as sub-Saharan Africa, where diverse RVA strains are circulating. Here, a plasmid-based reverse genetics system was used to generate simian RVA reassortants with VP4 and VP7 proteins derived from African human RVA strains not previously adapted to cell culture. We were able to rescue 1/3 VP4 mono-reassortants, 3/3 VP7 mono-reassortants, but no VP4/VP7 double reassortant. Electron microscopy showed typical triple-layered virus particles for the rescued reassortants. All reassortants stably replicated in MA-104 cells; however, the VP4 reassortant showed significantly slower growth compared to the simian RVA or the VP7 reassortants. The results indicate that, at least in cell culture, human VP7 has a high reassortment potential, while reassortment of human VP4 from unadapted human RVA strains with simian RVA seems to be limited. The characterized reassortants may be useful for future studies investigating replication and reassortment requirements of rotaviruses as well as for the development of next generation rotavirus vaccines.

Peer review of the pesticide risk assessment of the active substance Bacillus thuringiensis subsp. kurstaki strain SA-11.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Denmark, and co-rapporteur Member State, the Netherlands, for the pesticide active substance Bacillus thuringiensis subsp. kurstaki strain SA-11 and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of Bacillus thuringiensis subsp. kurstaki strain SA-11 as an insecticide on pome fruits (field use), protected tomato (including permanent greenhouses and walk-in tunnels) and turf (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Avaliação da ação neutralizante e da reatividade de anticorpos IgA e IgG anti-rotavírus SA-11 em soro de adultos saudáveis / Evaluation of neutralizing ability and reactivity of anti-rotavirus SA-11 IgA and IgG antibodies in serum samples from healthy adults

O rotavírus é a principal causa de diarréia em crianças em todo o mundo. Infecta também adultos, mas não há dados completos sobre a sua incidência nesse grupo nem sobre o papel de anticorpos preexistentes na proteção contra o vírus. O objetivo do trabalho foi avaliar a presença de anticorpos IgA e IgG anti-rotavírus SA-11, por ELISA, em amostras de soro de adultos saudáveis e sua ação neutralizante frente ao vírus, em ensaios de neutralização. Por Immunoblotting foi avaliado o reconhecimento de proteínas virais pelos anticorpos séricos. Observou-se que os títulos das amostras foram muito variáveis, sendo os de IgG superiores aos de IgA. Todas as amostras mostraram-se capazes de neutralizar o vírus em diferentes níveis, porém não foi possível estabelecer uma correlação com os títulos de anticorpos. Foi observado que anticorpos da classe IgG reconhecem mais proteínas virais que os da classe IgA. Este trabalho pode ser considerado mais um passo na elucidação do papel dos anticorpos séricos IgA e IgG anti-rotavírus na infecção em adultos.

Rotavirus has been considered the leading cause of diarrhea in children worldwide. The virus also infects adults but there is no conclusive data neither on the incidence of infection on this group nor on the role of pre-existing antibodies. The aim of the work was to evaluate the presence of anti-rotavirus SA-11 IgA and IgG by ELISA in serum samples of healthy adults and the serum neutralizing ability against the virus by neutralization assays. Immunoblotting was used to evaluate viral proteins recognition by serum antibodies. The antibody titers were extremely variable where IgG titers are greater than IgA ones. All samples were able to neutralize the virus in different levels but it was not possible to establish a correlation between antibody titers and neutralization ones. Immunoblotting assays revealed that IgG antibodies recognize more viral proteins than IgA did. This work can be considered a valuable step for elucidating the role of serum anti-rotavirus IgG and IgA antibodies in adults infection.