Introduction

The novel coronavirus, now officially designated as SARS-CoV-2, was first identified in Wuhan, Hubei Province, China in December of 2019. This virus has led to an outbreak of COVID-19 (Coronavirus Disease in 2019), which is associated with acute respiratory illness and infection, as is common for diseases caused by the coronavirus family. The World Health Organization’s (WHO) Emergency Committee declared the SARS-CoV-2 outbreak to be a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. The international community has been quick to respond with appropriate safety measures to minimize global spread of the virus.

Virologists worldwide have been ramping-up efforts to characterize the novel coronavirus – accelerated publications now becoming available on a daily basis - as researchers rush to understand its viral pathogenesis and create effective preventives and treatments. Herein, we provide a quick guide to the characterization research of SARS-CoV-2 and newly-available resources for all researchers who wish to participate in the global research initiative.

 

General Background on Coronaviruses

Coronaviruses, also known as Coronaviridae, are a large family of viruses that are common in mammals and birds. The rarer, but more commonly known, forms of coronaviruses include Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV), and, now, SARS-CoV-2. Coronaviruses are enveloped and known to have a positive-sense single-stranded RNA, or (+)ssRNA, genome. Individual virions, or virus particles, vary in infectivity and specificity depending on the composition of the inner core of nucleic acid (RNA) and the capsid protein shell, respectively. Researchers have already identified a common entry receptor between both SARS coronaviruses, with additional similarities having established these as closely-related viruses – bringing about the official name (SARS-CoV-2).

 

Characteristics of SARS-CoV-2

The initial source of the SARS-CoV-2 outbreak has yet to be confirmed, but given its high genetic similarity (96%) with the Rhinolophus affinis (bat) coronavirus (RaTG13) – higher than the 79.5% similarity found with SARS-CoV – a zoonotic origin is likely.3 SARS-CoV-2 is the seventh-known coronavirus to infect people (after 229E, NL63, OC43, HKU1, MERS, and SARS). The observation of sustained human-to-human transmission has shifted the focus to preventing spread through appropriate biosafety measures, especially in regards to travel.

The genome of the original SARS-CoV-2 strain has been identified as an RNA sequence of approximately 30k bases, with additional strains being genotyped and annotated for phylogenetic studies on an ongoing basis. Researchers in the US and China have independently demonstrated angiotensin-converting enzyme 2 (ACE2) as the receptor for entry. Previous structural analyses demonstrated key atomic-level interactions between the ACE2 host receptor and the SARS-CoV spike protein receptor-binding domain (RBD).  Given the similarities between both forms of SARS, below we discuss the requested research efforts, previous animal models used in SARS studies, and explore how custom model solutions could advance the global effort. Additional in-depth analyses are available in the “Related Resources” linked at the bottom of the page, including white papers and more.

 

Research Efforts for COVID-19 in the United States

The CDC’s SARS-CoV-2 isolate (grown in cell culture) will be available upon request from BEI Resources - once the culture is expanded – for researchers meeting the biosafety standards and suitable expertise, as required. This measure opens up several research opportunities for public & academic institutions, including:

  • Antiviral Development- Efficacy testing of antiviral medications in treating or preventing SARS-CoV-2 infections
  • Pathogenesis– Means of transmission to a host, illness severity, viral replication, dispersal to target organs, and mechanisms of shedding into the environment
  • Virus Stability – Assessing the virus’ ability to survive & remain viable under various conditions (in order to determine appropriate biosafety guidelines)1

 

Animal Models for Research in Virology and Infectious Disease

Transgenic mice expressing human ACE2 (hACE2) under the CAG promoter were previously developed to investigate the pathology of SARS-CoV, which (post-SARS-CoV infection) exhibited viral growth and pathology similar to that seen in humans.2 Such transgenic mice have been used in virology research as ‘humanized’ models for pathogenesis studies, development of vaccines, and evaluating therapeutics for both SARS and MERS – making them a formidable option for the study of SARS-CoV-2 infection.

Although most people have survived the initial COVID-19 infection, it is important to note that deaths among infected patients are caused by sequelae of the viral pneumonia – most commonly due to water in the lungs. Therefore, animal models of the disease pathology may be used to develop effective treatments to prevent death in severe cases of infection.

Mouse models are useful in research efforts across viral pathogenesis and disease pathology, serving as effective platforms for testing vaccines and antiviral therapies. As our way of contributing to the international epidemic prevention effort, we are opening service reservations on rodent models for SARS-CoV-2 research, including humanized host receptor targets ACE2, DPP4, and APN. Cyagen offers mouse models across several backgrounds, including FVB, C57BL/6, and newly-available BALB/c strains. Contact us today to inquire about your custom SARS-CoV-2 rodent mode. 

 

White Paper Technical Reviews Covering SARS-CoV-2

Our experts are proud to go beyond our routine animal model generation services to support the global research effort towards prevention and treatment of COVID-19; we are excited to share another White Paper featuring two technical reviews from our scientific team.

We are opening orders for select ACE2 mouse models and other hottest models for SARS-CoV-2 research.

 

Download the White Paper: Coronaviruses and SARS-CoV-2 – Host Receptor-Mediated Infection Mechanisms & Potential Antiviral Treatments

 

Outline of contents:

  1. Coronavirus Infection Mechanisms and Options for Antiviral Drug Research
  2. Interaction of Coronavirus Spike Protein with ACE2 Receptors Mediates Cellular Entry

 

References:

  1. CDC Grows SARS-CoV-2, the virus that causes COVID-19, in Cell Culture. (2020, February 15). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/about/grows-virus-cell-culture.html
  2. Gretebeck, Lisa M, and Kanta Subbarao. “Animal models for SARS and MERS coronaviruses.” Current opinion in virologyvol. 13 (2015): 123-9. doi:10.1016/j.coviro.2015.06.009
  3. Zhou, P., Yang, X., Wang, X. et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature(2020). https://doi.org/10.1038/s41586-020-2012-7
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