SARS-like WIV1-CoV poised for human emergence

By Vineet D. Menachery, B. Yount, Amy C. Sims, K. Debbink, S. Agnihothram, Lisa E. Gralinski, Rachel L. Graham, Trevor D. Scobey, Jessica A. Plante, S. Royal and 8 more. 2016

416 citations recorded by the source corpus.

Significance The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV highlights the continued risk of cross-species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS-like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1-CoV. Both full-length and chimeric WIV1-CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS-based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1-related viruses and the need for continued study and surveillance. Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.

Subfields: 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, positive): “Passive administration of these Abs protected mice from lethal challenges with MERS-CoV, SARS-CoV, and closely related viruses, indicating that they represent a promising therapeutic strategy against coronaviruses (Corti et al., 2015; Menachery et al., 2015; Menachery et al., 2016; Rockx et al., 200”
A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures (2020, methodology): “We also demonstrate that the Hfh4-ACE2 transgenic mouse model 21 supports efficient SARS-CoV-2 replication and pathogenesis in vivo.”
An Infectious cDNA Clone of SARS-CoV-2 (2020, background): “Using this approach, researchers have developed infectious clones for several coronaviruses, including SARS-CoV, MERS-CoV, and others (Menachery et al., 2015; Menachery et al., 2016; Scobey et al., 2013; Yount et al., 2003).”
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;”
Return of the Coronavirus: 2019-nCoV (2020, background): “More recent work has demonstrated that several bat CoVs are capable of infecting human cells without a need for intermediate adaptation [16,17].”
Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus (2017, background): “Protein-protein interactions can be modeled using a related homologous complex (19, 20) while reverse genetic strategies can test the permissiveness of human or other primate cells for infectious clones expressing the novel receptor binding domains or complete spike glycoprotein (21) (22) (23) (24) ”
Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion (2020, neutral): “Surveillance studies in bats detected numerous coronaviruses sharing high nucleotide sequence similarity with pathogenic human coronaviruses (Hu et al., 2017; Menachery et al., 2015, 2016), suggesting that additional zoonotic transmission events are likely to occur in the future.”
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, neutral): “A prerequisite for these viruses to jump to humans is the ability to efficiently bind human receptors (Becker et al., 2008; Letko et al., 2020; Menachery et al., 2015, 2016).”
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 .”
Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays (2020, background): “Indeed, for other coronaviruses, neutralizing antibodies are protective in mouse models of infection [16–20] and associated with at least some reduced susceptibility to re-infection or disease in humans [15,21,22].”
COVID-19 neutralizing antibodies predict disease severity and survival (2020, neutral): “One pre-emergent bat coronavirus, WIV1-CoV, is highly homologous to SARS-CoV and SARS-CoV-2 and can infect ACE2-expressing human cells (Menachery et al., 2016).”