SARS-like cluster of circulating bat coronavirus pose threat for human emergence

By Vineet D. Menachery, B. Yount, K. Debbink, S. Agnihothram, Lisa E. Gralinski, Jessica A. Plante, Rachel L. Graham, Trevor D. Scobey, Xingyi Ge, Eric F. Donaldson and 5 more. 2015

894 citations recorded by the source corpus.

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 mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

Subfields: Epidemiology, Infectious Diseases

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “As viruses similar to SARS-CoV (Menachery et al., 2015), MERSCoV (Anthony et al.”
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, background): “The recurrent spillovers of coronaviruses in humans along with detection of numerous coronaviruses in bats, including many SARS-related coronaviruses (SARSr-CoVs), suggest that future zoonotic transmission events may continue (Anthony et al., 2017; Ge et al., 2013; Hu et al., 2017; Li et al., 2005b;”
Structural insights into coronavirus entry (2019, background): “Numerous SARS-CoV and MERS-CoV-like viruses currently circulate in bats and dromedaries making outbreaks of highly pathogenic human CoVs a global health threat (Ge et al., 2013; Haagmans et al., 2014; Hu et al., 2017; Menachery et al., 2015 Menachery et al., , 2016 Sabir et al., 2016) .”
From SARS to MERS, Thrusting Coronaviruses into the Spotlight (2019, background): “Subsequently, certain SARS-CoV-like viruses found in bats demonstrated the ability to infect human cells without prior adaptation [7,8] which indicates the possibility of the re-emergence of SARS-CoV or SARS-CoV-like viruses.”
Animal models for COVID-19 (2020, background): “Pre-pandemic studies that assessed the potential emergence of SARS-like coronaviruses in bats indicated that some of these viruses were able to use several orthologues of human ACE2 for docking and entry 73,74 .”
An Infectious cDNA Clone of SARS-CoV-2 (2020, background): “We designed an in vitro ligation approach, similar to that used for constructing the infectious clones of SARS-CoV andMERS-CoV (Scobey et al., 2013; Yount et al., 2003), to directionally assemble the full-length complimentary DNA (cDNA) of the SARS-CoV-2 genome (Figure 1A).”
Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic (2020, background): “Early detection via genomics and sequencing was not possible during SE Asia's initial outbreaks of avian influenza H5N1 (1997, (2003) (2004) (Ge et al., 2013; Menachery et al., 2015 Menachery et al., , 2016 , appropriate measures should have been in place for outbreaks of novel coronaviruses.”
A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV (2020, background): “As this coronavirus outbreak continues to 158 pose an enormous global risk (33, 34), the availability of conserved epitopes may allow 159”
A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures (2020, result): “We compared the ACE2-contacting residues in the RBDs of S proteins from several group 2B coronaviruses capable of infecting mice with those of SARS-CoV-2 21,25,26 (Fig.”
Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis (2018, background): “These viruses are poised for emergence because they both efficiently use human ACE2 entry receptors and resist existing vaccines and immunotherapeutics (6, 7).”
Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus (2017, background): “And while pseudotypes are not always accurate predictors of spike glycoprotein function (23), these findings indicate that multiple cell-entry strategies could exist for”