A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

  title={A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence},
  author={Vineet D. Menachery and Boyd L. Yount and Kari Debbink and Sudhakar S. Agnihothram and Lisa E. Gralinski and Jessica A. Plante and Rachel L. Graham and Trevor D. Scobey and Xingyi Ge and Eric Donaldson and Scott H. Randell and Antonio Lanzavecchia and Wayne A. Marasco and Zh{\`e}ngl{\`i} Sh{\'i} and Ralph S. Baric},
  journal={Nature Medicine},
  pages={1508 - 1513}
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a… 

Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

The importance of the conserved 2′O-MTase activity for CoV pathogenesis is demonstrated and NSP16 is highlighted as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting.

SARS-CoV-2 Infection is Effectively Treated and Prevented by EIDD-2801

The results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II-III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19.

Severe acute respiratory syndrome (SARS) related coronavirus in bats

The current knowledge of CoVs on geographical distribution, genetic diversity, cross-species transmission potential and possible pathogenesis in humans is summarized for a better understanding of bat SARS-related CoVs in the context of prevention and control.

The next SARS?

It is suggested that CoVs currently circulating in bats have the potential for human emergence and currently available therapeutics (monoclonal antibodies and vaccines) failed to protect mice from viral infection.

Understanding bat SARS-like coronaviruses for the preparation of future coronavirus outbreaks — Implications for coronavirus vaccine development

This study presents concrete evidence that bats are the origin and natural reservoir of SARS-CoV, and the knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.

Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801

The results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment ofCO VID-19.

Infection of bat and human intestinal organoids by SARS-CoV-2

Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.

A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures

A model in mouse using a species-adapted virus recapitulates features of SARS-CoV-2 infection and age-related disease pathogenesis in humans, and provides a model system for rapid evaluation of medical countermeasures against coronavirus disease 2019 (COVID-19).

Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge

It is demonstrated that SARS- coV-2–infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronvirus (CoV) strains.



Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

These results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs, and highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots.

Mechanisms of Zoonotic Severe Acute Respiratory Syndrome Coronavirus Host Range Expansion in Human Airway Epithelium

The data suggest that the human adaptation of zoonotic SARS-CoV strains may select for some variants that are highly susceptible to select MAbs that bind to RBDs.

Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin

This study investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat, and found it to be largely compatible with SARS- coV S protein both in structure and in function.

Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants

The comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge is reported, identifying gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations.

Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

The design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic is reported.

Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

R reverse genetics and the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals.

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

It is demonstrated that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following Bt coVHKU5-SE challenge, and an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs is identified.

Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China

Diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV are identified in bats collected in Yunnan, China, indicating that most reported bat SARS-like CoVs are not the progenitors of human Sars CoV.

Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission

This review discusses the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model to pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emerged of coronaviruses in new host populations.

Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus

These data provide a mechanism for overcoming neutralization escape by use of broadly cross- reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor-binding domain that are critical for virus replication and virulence.