scholarly journals The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry.

2022 ◽  
Author(s):  
Thomas P. Peacock ◽  
Jonathan C Brown ◽  
Jie Zhou ◽  
Nazia Thakur ◽  
Joseph Newman ◽  
...  

At the end of 2021 a new SARS-CoV-2 variant, Omicron, emerged and quickly spread across the world. It has been demonstrated that Omicrons high number of Spike mutations lead to partial immune evasion from even polyclonal antibody responses, allowing frequent re-infection and vaccine breakthroughs. However, it seems unlikely these antigenic differences alone explain its rapid growth; here we show Omicron replicates rapidly in human primary airway cultures, more so even than the previously dominant variant of concern, Delta. Omicron Spike continues to use human ACE2 as its primary receptor, to which it binds more strongly than other variants. Omicron Spike mediates enhanced entry into cells expressing several different animal ACE2s, including various domestic avian species, horseshoe bats and mice suggesting it has an increased propensity for reverse zoonosis and is more likely than previous variants to establish an animal reservoir of SARS-CoV-2. Unlike other SARS-CoV-2 variants, however, Omicron Spike has a diminished ability to induce syncytia formation. Furthermore, Omicron is capable of efficiently entering cells in a TMPRSS2-independent manner, via the endosomal route. We posit this enables Omicron to infect a greater number of cells in the respiratory epithelium, allowing it to be more infectious at lower exposure doses, and resulting in enhanced intrinsic transmissibility.

2021 ◽  
Author(s):  
Jiri Zahradnik ◽  
Aekkachai Tuekprakhon ◽  
Helen M Ginn ◽  
Helen M.E. Duyvesteyn ◽  
Mohammad Bahar ◽  
...  

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to high-affinity binding to ACE2, including mutations Q498R and N501Y critical in forming additional interactions in the interface. Together with increased charge complementarity between the RBD and ACE2, these substantially increase affinity and potentially virus transmissibility through increased syncytia formation. Further mutations promote immune evasion. We have studied the binding of a large panel of potent monoclonal antibodies generated from early pandemic or Beta infected cases. Mutations in Omicron will likely compromise the binding of many of these and additionally, the binding of antibodies under commercial development, however residual binding should provide protection from severe disease.


Author(s):  
Loïc Epelboin ◽  
Carole Eldin ◽  
Pauline Thill ◽  
Vincent Pommier de Santi ◽  
Philippe Abboud ◽  
...  

Abstract Purpose of Review In this review, we report on the state of knowledge about human Q fever in Brazil and on the Guiana Shield, an Amazonian region located in northeastern South America. There is a contrast between French Guiana, where the incidence of this disease is the highest in the world, and other countries where this disease is practically non-existent. Recent Findings Recent findings are essentially in French Guiana where a unique strain MST17 has been identified; it is probably more virulent than those usually found with a particularly marked pulmonary tropism, a mysterious animal reservoir, a geographical distribution that raises questions. Summary Q fever is a bacterial zoonosis due to Coxiella burnetii that has been reported worldwide. On the Guiana Shield, a region mostly covered by Amazonian forest, which encompasses the Venezuelan State of Bolivar, Guyana, Suriname, French Guiana, and the Brazilian State of Amapá, the situation is very heterogeneous. While French Guiana is the region reporting the highest incidence of this disease in the world, with a single infecting clone (MST 117) and a unique epidemiological cycle, it has hardly ever been reported in other countries in the region. This absence of cases raises many questions and is probably due to massive under-diagnosis. Studies should estimate comprehensively the true burden of this disease in the region.


mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Denise McAloose ◽  
Melissa Laverack ◽  
Leyi Wang ◽  
Mary Lea Killian ◽  
Leonardo C. Caserta ◽  
...  

ABSTRACT Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species. IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.


Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 244 ◽  
Author(s):  
Jiabao Xu ◽  
Shizhe Zhao ◽  
Tieshan Teng ◽  
Abualgasim Elgaili Abdalla ◽  
Wan Zhu ◽  
...  

After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.


2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Louise A. Rollins-Smith ◽  
Antonio C. Ruzzini ◽  
J. Scott Fites ◽  
Laura K. Reinert ◽  
Emily M. Hall ◽  
...  

ABSTRACTAmphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungusBatrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses againstB. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced byB. dendrobatidis. SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 μM and is found at concentrations between 1 and 10 μM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 μM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 μM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 μM. We interpret these results to suggest thatB. dendrobatidisproduces an “armamentarium” of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system.


2021 ◽  
Author(s):  
Wei Lin Lee ◽  
Xiaoqiong Gu ◽  
Federica Armas ◽  
Fuqing Wu ◽  
Franciscus Chandra ◽  
...  

On November 26, 2021, the B.1.1.529 COVID-19 variant was named as the Omicron variant of concern. Reports of higher transmissibility and potential immune evasion triggered flight bans and heightened health control measures across the world to stem its distribution. Wastewater-based surveillance has demonstrated to be a useful complement for community-based tracking of SARS-CoV-2 variants. Using design principles of our previous assays that detect SARS-CoV-2 variants (Alpha and Delta), here we report an allele-specific RT-qPCR assay that simultaneously targets mutations Q493R, G496S and Q498R for quantitative detection of the Omicron variant in wastewater. This method is open-sourced and can be implemented using commercially available RT-qPCR protocols, and would be an important tool for tracking the spread and introduction of the Omicron variant in communities for informed public health responses.


Author(s):  
Steven James

An open question in artificial intelligence is how to learn useful representations of the real world. One approach is to learn symbols, which represent the world and its contents, as well as models describing the effects on these symbols when interacting with the world. To date, however, research has investigated learning such representations for a single specific task. Our research focuses on approaches to learning these models in a domain-independent manner. We intend to use these symbolic models to build even higher levels of abstraction, creating a hierarchical representation which could be used to solve complex tasks. This would allow an agent to gather knowledge over the course of its lifetime, which could then be leveraged when faced with a new task, obviating the need to relearn a model every time a new unseen problem is encountered.


2021 ◽  
Author(s):  
Paola Stefanelli ◽  
Filippo Trentini ◽  
Giorgio Guzzetta ◽  
Valentina Marziano ◽  
Alessia Mammone ◽  
...  

SARS-CoV-2 variants of concern (B.1.1.7, P.1 and B.1.351) have emerged in different continents of the world. To date, little information is available on their ecological interactions. Based on two genomic surveillance surveys conducted on February 18 and March 18, 2021 across the whole Italian territory and covering over 3,000 clinical samples, we found significant co-circulation of B.1.1.7 and P.1. We showed that B.1.1.7 was already dominant on February 18 in a majority of regions/autonomous provinces (national prevalence 54%) and almost completely replaced historical lineages by March 18 (dominant in all regions/autonomous provinces, national prevalence 86%). At the same time, we found a substantial proportion of cases of the P.1 lineage on February 18, almost exclusively in Central Italy (with an overall prevalence in the macro-area of 18%), which remained at similar values on March 18, suggesting the inability by this lineage to outcompete B.1.1.7. Only 9 cases from variant B.1.351 were identified in the two surveys. At the national level, we estimated a mean relative transmissibility of B.1.1.7 (compared to historical lineages) ranging between 1.55 and 1.57 (with confidence intervals between 1.45 and 1.66). The relative transmissibility of P.1 estimated at the national level varied according to the assumed degree of cross-protection granted by infection with other lineages and ranged from 1.12 (95%CI 1.03-1.23) in the case of complete immune evasion by P.1 to 1.39 (95%CI 1.26-1.56) in the case of complete cross-protection. These observations may have important consequences on the assessment of future pandemic scenarios. 


JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 1-2
Author(s):  
Rafi A Jan ◽  
Arif Rehman Sheikh

The world is yet again challenged by the outbreak of a new coronavirus, named SARS-CoV-2; disease caused by this virus, now termed as COVID-19,was first reported in Wuhan City, Hubei Province China in the last week of December 2019. As of march 5, WHO reports a total of 80,430 cases of COVID-19 with 3013 deaths from China. The disease has been now reported in all the continents of the world except Antarctica –around 15,053 cases in 85 countries with 273 deaths. Although many cases have been reported in India, whether it going to touch this part of the country too, only time will tell.  It is very likely that by the time this editorial goes in print, the numbers would have changed significantly. It is because of this developing outbreak situation that has engulfed the entire world and has the potential to turn into a pandemic, I decided to focus on this new disease than to comment on one of the many well written papers in this issue of the journal. Understanding of this novel coronavirus, SARS-CoV-2, is evolving. This virus belongs to a large family of viruses known as coronaviridae family which are enveloped positive stranded RNA viruses causing respiratory and enteric infections affecting both animals and humans. The animal species infected by various coronaviruses include camels, cattle, cats and bats. Although very uncommon, coronaviruses of animal origin can infect humans and then spread from person to person, sometimes with devastating morbidity and mortality as is the case with MERS-CoV. The other two animal coronaviruses infecting people are SARS-CoV and SARS-CoV-2. All these three viruses are betacoronaviruses and have their origin in bats1. Sequences from SARS-CoV-2 generated from patients outside China are similar to the original Chinese isolate suggesting a likely single emergence of SARS-CoV-2 from an animal reservoir. In the coming months we expect to learn more about the evolution and other pathogenetic aspects of the disease caused by SARS-CoV-2


2021 ◽  
Author(s):  
Venkata-Viswanadh Edara ◽  
Lilin Lai ◽  
Malaya Sahoo ◽  
Katharine Floyd ◽  
Mamdouh Sibai ◽  
...  

SARS-CoV-2 has caused a devastating global pandemic. The recent emergence of SARS-CoV-2 variants that are less sensitive to neutralization by convalescent sera or vaccine-induced neutralizing antibody responses has raised concerns. A second wave of SARS-CoV-2 infections in India is leading to the expansion of SARS-CoV-2 variants. The B.1.617.1 variant has rapidly spread throughout India and to several countries throughout the world. In this study, using a live virus assay, we describe the neutralizing antibody response to the B.1.617.1 variant in serum from infected and vaccinated individuals. We found that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. This suggests that protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. As the B.1.617.1 variant continues to evolve, it will be important to monitor how additional mutations within the spike impact antibody resistance, viral transmission and vaccine efficacy.


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