Complete Genome Sequence and Phylogenetic Analysis of a Goose Astrovirus Isolate in China

Astroviruses are considered the cause of gastroenteritis in humans and animals. Studies in recent years show avian astroviruses are also associated with duckling hepatitis, gosling gout, and chicken nephritis. In this study, a GAstV strain, designated as JS2019/China, was detected in dead goslings from a commercial goose farm in Jiangsu province of China. Viral strain was proliferated in goose embryos and sequence analysis showed the isolated strain had a classical structure arrangement and a series of conserved regions compared with other GAstVs. Sequence comparison and phylogenetic analysis of whole genome and ORF2 revealed that JS2019/China belongs to the GAstV group-1, which consists of most of the GAstV strains. Amino acid analysis indicated that some mutants might have an impact on viral protease capacity, such as V505I and K736E of ORF1a and T107I, F342S, and S606P of ORF2. Taken together, a novel GAstV strain was isolated and genomic analysis and protein polymorphism analysis indicated that some amino acid mutants might affect the viral virulence.

GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition

Since December 2019, SARS-CoV-2 has spread quickly worldwide, leading to more than 280 million confirmed cases, including over 5,000,000 deaths. Interestingly, coronaviruses were found to subvert and hijack autophagic process to allow their viral replication. Autophagy-modulating compounds thus rapidly emerged as an attractive strategy to fight SARS-CoV-2 infection, including the well-known chloroquine (CQ). Here, we investigated the antiviral activity and associated mechanism of GNS561/Ezurpimtrostat, a small lysosomotropic molecule inhibitor of late-stage autophagy. Interestingly, GNS561 exhibited antiviral activity of 6–40 nM depending on the viral strain considered, currently positioning it as the most powerful molecule investigated in SARS-CoV-2 infection. We then showed that GNS561 was located in lysosome-associated-membrane-protein-2-positive (LAMP2-positive) lysosomes, together with SARS-CoV-2. Moreover, GNS561 increased LC3-II spot size and caused the accumulation of autophagic vacuoles and the presence of multilamellar bodies, suggesting that GNS561 disrupted the autophagy mechanism. To confirm our findings, we used the K18-hACE2 mouse model and highlighted that GNS561 treatment led to a decline in SARS-CoV-2 virions in the lungs associated with a disruption of the autophagy pathway. Overall, our study highlights GNS561 as a powerful drug in the treatment of SARS-CoV-2 infection and supports the hypothesis that autophagy blockers could be an alternative strategy for COVID-19.

Comprehensive Contact Tracing, Testing and Sequencing Show Limited Transmission of SARS-CoV-2 between Children in Schools in Norway, August 2020 to May 2021

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools has been a topic of controversy. In this study among school contacts of SARS-CoV-2 positive children in 43 contact-investigations, we investigated SARS-CoV-2 transmission in Norway, August 2020–May 2021. All participants were tested twice within seven to ten days, using SARS-CoV-2 PCR on home-sampled saliva. Positive samples were whole genome sequenced. Among the 559 child contacts, eight tested positive (1.4%, 95% CI 0.62–2.80), with no significant difference between primary (1.0%, 95% CI 0.27–2.53) and secondary schools (2.6%, 95% CI 0.70–6.39), p = 0.229, nor by viral strain, non-Alpha (1.4%, 95% CI 0.50–2.94) and Alpha variant (B.1.1.7) (1.7%, 95% CI 0.21–5.99), p = 0.665. One adult contact (1/100) tested positive. In 34 index cases, we detected 13 different SARS-CoV-2 Pango lineage variants, with B.1.1.7 being most frequent. In the eight contact-investigations with SARS-CoV-2 positive contacts, four had the same sequence identity as the index, one had no relation, and three were inconclusive. With mitigation measures in place, the spread of SARS-CoV-2 from children in schools is limited. By excluding contact-investigations with adult cases known at the time of enrolment, our data provide a valid estimate on the role of children in the transmission of SARS-CoV-2 in schools.

Contact transmission of SARS-CoV-2 on fomite surfaces: surface survival and risk reduction

There is an unprecedented concern regarding the viral strain SARS-CoV-2 and especially its respiratory disease more commonly known as COVID-19. SARS-CoV-2 virus has the ability to survive on different surfaces for extended periods, ranging from days up to months. The new infectious properties of SARS-CoV-2 vary depending on the properties of fomite surfaces. In this review, we summarize the risk factors involved in the indirect transmission pathways of SARS-CoV-2 strains on fomite surfaces. The main mode of indirect transmission is the contamination of porous and non-porous inanimate surfaces such as textile surfaces that include clothes and most importantly personal protective equipment like personal protective equipment kits, masks, etc. In the second part of the review, we highlight materials and processes that can actively reduce the SARS-CoV-2 surface contamination pattern and the associated transmission routes. The review also focuses on some general methodologies for designing advanced and effective antiviral surfaces by physical and chemical modifications, viral inhibitors, etc.

Rapid Global Spread of the SARS-CoV-2 Delta (B.1.617.2) Variant: Spatiotemporal Variation and Public Health Impact

The COVID-19 pandemic has already affected human society for more than 1.5 years. As of August 8, 2021, this pandemic had caused more than 203 million infected and 4.3 million deaths worldwide. As an RNA virus, SARS-CoV-2 is prone to genetic evolution, thus resulting in development of mutations over time. Numerous variants of SARS-CoV-2 have been described globally, four of which are considered variants of concern (VOCs) by the WHO: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1) and Delta (B.1.617.2). The Delta VOC was first reported in India in December of 2020 and has since affected approximately 130 different countries and regions. Herein, the spatiotemporal spread of the Delta VOC during April to July 2021 in 20 selected countries with available data were analyzed. The prevalence of the Delta VOC sequences was maintained at low levels in the beginning of April, increased rapidly in the following 3 months and is now becoming the predominant viral strain in most regions of the world. We also discuss the effects of the Delta VOC on transmissibility, clinical severity and vaccine effectiveness according to the latest data. The Delta VOC has greater transmissibility and risk of hospitalization than the ancestral SARS-CoV-2 strains and the other three VOCs. The Delta VOC places partially or unvaccinated sub-populations at high risk. Currently authorized vaccines, regardless of vaccine type, still have reliable effectiveness against symptomatic infections and hospitalizations due to the Delta VOC.

Phytochemical Analysis of Ashwagandha (Withania Somnifera) and its Role on Covid-19 –A Qualitative Review

COVID-19 being a mild to severe respiratory and an infectious disease is caused by a new viral strain named coronavirus 2 (SARS-CoV-2). Though managed with antivirals such as lopinavir, ritonavir and nelfinavir, as well as the antimalarials chloroquine and hydroxychloroquine etc, none of them have provided the promising solution. Amidst these conventional approaches, bioactive natural compounds are being considered due to its good biocompatibility, bioavailability, less toxicity and rich phyto-constituents like phenols, steroids and flavonoid molecules etc. Ayurvedic system of medicine is the Ancient medicine that is being practiced since 5000yrs ago and Ashwagandha or Withania somnifera is being used as a rasayana in traditional medicine systems like Ayurveda, Unani, and Siddha. This has been known for its therapeutic benefits since long period including anticancer properties, neuro-protective, cardio-protective, hepato-protective, anti-inflammatory, anti-diabetic, antimicrobial, anti-arthritic, antistress/adaptogenic, chemo-/radiation sensitizing and immuno-modulatory properties etc. Currently Ashwagandha has been extensively studied using molecular docking approaches on Covid-19 due to its immuno-modulatory properties and Withania somnifera could be developed as a therapeutic agent against COVID-19 for both management and prevention.

Inferring viral occurrence patterns through a synthetic data simulation

Viruses infecting humans are manifold and several of them provoke significant morbidity and mortality. Simulations creating large synthetic datasets from observed multiple viral strain infections in a limited population sample can be a powerful tool to infer significant pathogen occurrence and interaction patterns, particularly if limited number of observed data units is available. Here, to demonstrate diverse human papillomavirus (HPV) strain occurrence patterns, we used log-linear models combined with Bayesian framework for graphical independence network (GIN) analysis. That is, to simulate datasets based on modeling the probabilistic associations between observed viral data points, i.e different viral strain infections in a set of population samples. Our GIN analysis outperformed in precision all oversampling methods tested for simulating large synthetic viral strain-level prevalence dataset from observed set of HPVs data. Altogether, we demonstrate that network modeling is a potent tool for creating synthetic viral datasets for comprehensive pathogen occurrence and interaction pattern estimations.

CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.

Modeling the evolution of SARS-CoV-2 under non-pharmaceutical interventions

Social and behavioral non-pharmaceutical interventions (NPIs), such as mask-wearing, social distancing, and travel restrictions, as well as diagnostic tests, have been broadly implemented in response to the COVID-19 pandemic. Epidemiological models and data analysis affirm that wide adoption of NPIs helps to control the pandemic. However, SARS-CoV-2 has extensively demonstrated its ability to evolve. Therefore, it is crucial to examine how NPIs may affect the evolution of the virus. Such evolution could have important effects on the spread and impact of the pandemic.We used evo-epidemiological models to examine the effect of non-pharmaceutical interventions and testing on two evolutionary trajectories for SARS-CoV-2: attenuation and test evasion. Our results show that when stronger measures are taken, selection may act to reduce virulence. Additionally, the timely application of NPIs could significantly affect the competition between viral strains, favoring reduced virulence. Furthermore, a higher testing rate can select for a test-evasive viral strain, even if that strain is less infectious than the detectable competing strain. Importantly, if a less detectable strain evolves, epidemiological metrics such as confirmed daily cases may distort our assessment of the pandemic. Our results highlight the important implications NPIs can have on the evolution of SARS-CoV-2.