The current COVID-19 pandemic is caused by SARS-CoV-2, a coronavirus related to the SARS-CoV virus which caused the global SARS outbreak in 2003. The COVID-19 has engulfed the whole world with new outbreaks and re-emergence and no end in sight. Researchers and innovators from industry and academia are racing to develop vaccines and therapeutics to combat the COVID-19 pandemic. They need relevant in vitro screening assays and in vivo animal models to understand the disease pathology and develop safe and efficacious therapeutics and vaccines against SARS-CoV-2
Coronaviruses are enveloped viruses containing a single-stranded positive sense RNA genome. The viral genome encodes enzymes and structural proteins necessary for the replication and production of progeny viruses following infection of a susceptible cell. The virally-encoded Spike glycoprotein (S) mediates infection of cells through interaction with a specific cellular target molecule, often referred to as the viral receptor. The SARS-CoV-2 S-protein is 76% identical to that of SARS-CoV which led to the hypothesis and realization that SARS-CoV-2 utilizes the same viral receptor, the human angiotensin-converting enzyme 2 (hACE-2), as SARS-CoV. Both S glycoproteins have two subdomains- S1 and S2. S1 domain contains the receptor binding site and is required for attachment to hACE-2, while the S2 domain is involved in membrane fusion. The two subdomains must be separated by proteolytic cleavage for efficient infection to occur and the presence of a furin cleavage site between the S1 and S2 domains in SARS-CoV-2, which is not present in the most closely related bat coronavirus or SARS-CoV, may help to explain the “jump” from bat to human and the increased human to human transmissibility between SARS-CoV-2 and SARS-CoV.
A major hurdle for COVID-19 researchers developing therapeutics and vaccine is lack of relevant animal models. Advancing new vaccines and therapeutics into human trials without safety and efficacious animal model studies poses a high unmitigated safety risk to clinical trial participants. Transgenic mice expressing hACE2 receptor are not expected to be available for 3-4 months, and the necessity to work with the virus as a BSL-3 pathogen poses additional challenges.
To overcome these limitations and expedite the development of COVID-19 vaccines and antiviral therapeutics, Noble Life Sciences has in vitro testing capabilities as well as in vivo models that are currently under development. Noble is developing a novel proprietary mouse model as a rapid alternative to the above transgenic mice. The model is under validation for high-capacity use in vaccine development with pseudotyped viral reporter particles bearing the viral spike protein under BSL-2 conditions and for antiviral therapeutic development using wild-type SARS-CoV-2 under BSL-3 conditions.
Noble Life Sciences support infectious disease scientists in their research and discovery of therapeutics and vaccines to fight emerging and re-emerging viral and bacterial pathogens. We have a panel of optimized animal models for viral and bacterial infections that can be leveraged to study the efficacy of candidate drugs, explore drug toxicity and validate biomarkers.