ACE2 nanoparticles prevent cell entry of SARS-CoV-2 (preprint)

We have now been in the grip of the COVID-19 pandemic for over two years with devastating consequences. The continual evolution of the virus has challenged the efficacy of many vaccines and treatment options based on immunotherapies are compromised by this viral escape. One treatment strategy that averts viral escape is the use of constructs based on its entry receptor Angiotensin-Converting Enzyme 2 (ACE2) acting as decoys. Here, we combined full-length human ACE2 with viral vectors commonly used for gene therapy to form nanoparticles that present ACE2 on their surface analogous to human cells. Using cell-based assays and direct, multiscale imaging including cryogenic cellular tomography, we show that these ACE2 nanoparticles are highly efficient in preventing entry of SARS-CoV-2, the virus causing COVID-19, in model cell systems as well as human respiratory tract ex-vivo cultures. Thus, ACE2 nanoparticles have high potential as the next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.

Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters (preprint)

A pandemic caused by the novel SARS-CoV-2 virus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats is spreading across the world and impacting the healthcare systems and global economy1,2. A suitable small animal model is urgently needed to support the development of vaccines and antiviral treatments against the SARS-CoV-2 virus. We report the pathogenesis and transmissibility of the SARS-CoV-2 in the golden Syrian hamster model. The SARS-CoV-2 virus replicated in the epithelial cells of respiratory and gastrointestinal tracts. Immunohistochemistry demonstrated viral antigens in the areas of lung consolidation on day 2 and 5 post- inoculation, followed by rapid viral clearance and tissue repairing on day 7. Viral antigen was also detected in the epithelial cells of duodenum without apparent inflammatory response on day 2. Notably, we observed that the SARS-CoV-2 virus can be transmitted efficiently from the inoculated hamsters to co-housed naïve contact hamsters. The inoculated hamsters and naturally-infected hamsters lost greater than 10% of the body weight, and all animals recovered with the detection of neutralizing antibodies within 14 days. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in human patients with mild infections.Authors Sin Fun Sia, Li-Meng Yan, and Alex WH Chin contributed equally to this work.