Testing Hydroxychloroquine Inhibition on Covid-19 on Syrian Hamsters
- Sanaa Kirpalani
- Jun 14, 2024
- 3 min read
The drug hydroxychloroquine (HCQ) was found to be efficient in inhibiting the 2003 Severe acute respiratory syndrome (SARS) outbreak and showed promising capability for the Coronavirus Outbreak of 2019. The model organisms used to test HCQ for its effectiveness with SARS-Covid-19 were the Macaca mulatta (Macaques) and the Mesocricetus auratus (Syrian Hamster).
The Syrian Hamster was chosen to model the respiratory response to HCQ on SARS-COVID-19 due to the resembled lung pathology responses they have to humans with COVID-19 when the Hamsters are infected with SARS-CoV-2. Elevated cholesterol, triglycerides, lipoproteins, and similar metabolic markers were all observed in both humans with COVID-19 and Syrian Hamsters with SARS-CoV-2. Hamsters have a gestation period of 16 days, are generally low cost, low maintenance, small in size (averaging about 7 inches long and 120 grams), are susceptible to many metabolic disorders and pathogens, and possess physical features- such as an easily manipulated and everted cheek pouch- that increase the scope of study which can be performed during testing. All of these factors further allow researchers to feel confident in the decision to test HCQ on Syrian Hamsters. The only big caveat is that not many are left in the world because it is a protected species. Due to the suddenness of Covid-19, HCQ was given emergency approval for use in patients with the virus, but more testing had to be done. Once the Syrian Hamsters were identified as the best, most accurate model organism, the in vitro efficacy was tested by observing if the HCQ had an inhibitory effect on SARS-CoV-2 in Vero E6 cells. The drug concentration varied and the viral RNA load was traced using reverse transcriptase polymerase chain reaction (qRT-PCR). The half-maximal concentration value of HCQ in the cells showed low levels of 164.7 nM consistent with previous studies with effective inhibitory responses of HCQ of SARS-CoV-2 replication. The next step would be to test HCQ’s ability to redirect the course of SARS-CoV-2 by testing the Hamsters. HCQ would be administered either 24 hours before the infection or 1 hour after. Either treatment included a low dose of 6.5 mg/kg in phosphate-buffered saline (PBS) of HCQ, a high dose of 50.0 mg/kg in PBS of HCQ, or a control group treated with vehicle only. All would receive a 1×10^4 dose of SARS-CoV-2 and treatment would continue for 3 days, which is the ideal time for clinical signs to increase. Signs such as ruffled hair, increased respiratory rate, and reduced mobility were all observed around the 3rd post-infection day. qRT-PCR oral and rectal swab samples showed virus replication and shedding on days 2 and 4 of the treatment, showing high genome copies in the oral swabs(>10^7 copies/ mL) and lower in the rectal swabs(<10^6 copies/ mL). Viral lung genome was high on day 4 being 10^14 genome copies/ g. Lung to body ratio was similar in all Hamsters at the end of the trial with no major differences between any of the groups. Overall, HCQ showed little to no significant impact on SARS-CoV-2 replication and shedding as well as no disease manifestation or progression. Similar testing on Macaques also showed no statistical significance(p=0.004) between the groups and signs of illness did not decrease during the 7 consecutive days of testing. Physical changes similar to the Syrian Hamster, such as ruffled fur, pale appearance, increased respiratory activity, and reduced appetite, were observed in the Macaque during testing with no sign of decreased viral RNA replication.
In conclusion, HCQ has shown minimal effects in inhibiting the replication of SARS-CoV-2 in the Syrian Hamster or the Macaque. A slight difference in the results of the tested model organism groups signified no statistically significant impact of HCQ on the viral RNA and the inhibition of its replication. Results such as these support the conclusion that HCQ is ineffective and further testing will most probably not be required.
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