Evaluating the Efficacy of a SARS-CoV-2 Preventative Drug in a Syrian Hamster Model

Patricia Boley
Category: 
Staff Researcher
Advisor: 
Scott Kenney
Department: 
Center for Food Animal Health
Abstract: 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus similar to SARS-CoV and to betacoronaviruses that have been detected in other species, has spread across the world with dire effects on healthcare systems and economies. Suitable small animal models are needed to support the development of vaccines and other therapies. Here we report the efficacy of compound X in the reduction of morbidity and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Compound X is an FDA approved proprietary drug that has exhibited the ability to kill the SARS-2-CoV in cell culture systems, as determined by a reduction in virus titer upon treatment measured via median tissue culture infective dose assays (TCID50). In experiment one we established baseline infectivity of the SARS-CoV-2 USA-WA1/2020 isolate in inoculated hamsters, and its ability to transmit to sentinel hamsters comingled with inoculated hamsters 1 day post infection. Baseline body weights and temperatures were measured before infection and monitored daily for the duration of the experiment. We monitored the presence of infectious virus in nasal mucosa via nasal wash, bronchial epithelial cells via lung lavage and areas of lung consolidation on days 3 and 7 after inoculation with SARS-CoV-2. We found live virus in epithelial cells of lung, trachea and nasal turbinates as determined by TCID50. SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact. Inoculated and comingled sentinel hamsters showed weight loss post-inoculation or post-contact. In experiment 2, the sentinel hamsters began treatment with compound X 48 hours prior to comingling with infected hamsters and continued treatment through the duration of the experiment while cohoused with an infected hamster. Treatment with compound X consisted of 25 µl per nostril every 12 hours. Other than the treatment with compound X, experiment 2 was conducted in the same manner as experiment 1. We show that SARS-CoV-2 USA-WA1/2020 is transmissible in hamsters and causes gross lung pathology. Initial data suggests compound X was unable to prevent SARS-CoV-2 transmission under conditions of extended cohabitation of infected animals.