The study compares the effects of hydroxychloroquine and favipiravir on SARS-CoV-2 infected hamsters.

Review by Emily Henderson, Bachelor of ScienceOctober 9, 2020

Virologists at the Lega Institute have shown that the antimalarial drug hydroxychloroquine does not limit SARS-CoV-2 coronavirus replication in hamsters. In contrast, the high-dose favipiravir anti-influenza drug has antiviral effects on hamsters. The team published the findings in the minutes of the National Academy of Sciences (PNAS).

Virologists at the KU Leuven Rega Institute are working on two lines of SARS-CoV-2 research. Searching for vaccines to prevent infection and testing existing drugs that can reduce the viral load of infected people.

Testing Effectiveness of Vaccines and antivirals are preclinical, and researchers are using hamsters. Rodents are particularly well suited for SARS-CoV-2 studies because the virus replicates strongly in hamsters after infection. In addition, hamsters develop lung lesions similar to mild COVID-19 in humans. For example, this is not the case for mice.

In this study, a team of Professors Suzanne Kaptein (PhD), Joana Rocha-Pereira (PhD), Professor Leen Delang, and Professor Johan Neyts teamed up on hydroxychloroquin or favipiravir, a widespread antiviral drug used in Japan to treat influenza. I gave one of them to the hamster. 4-5 days. They tested several doses of favipiravir. Hamsters were infected with the SARS-CoV-2 virus in two ways. High doses of the virus can be inserted directly into the nose, or healthy hamsters can be placed in cages containing infected hamsters.

Drug treatment was started 1 hour before direct infection or 1 day before exposure to infected hamsters. Four days after infection or exposure, researchers measured the amount of virus present in hamsters.

Hydroxychloroquine vs favipiravir

Treatment with hydroxychloroquine had no effect: viral levels did not decrease and the hamster was still infectious.

Many COVID-19 patients are already treated with hydroxychloroquine, despite the lack of clear evidence in animal models and clinical studies. Based on these results and the results of other teams, it is not advisable to further investigate the use of hydroxychloroquine as a treatment for COVID-19. “

Joana Rocha-Pereira, Virologists, KU Leuven Rega Institute

However, high doses of favipiravir had a strong effect. A few days after infection, virologists received this dose and found few infectious viral particles in hamsters infected in the nasal passages. In addition, hamsters that were caged and dosed with infected hamsters did not develop an overt infection. After sharing the cage with the infected hamster, everyone who did not receive the drug became infected.

A low-dose favipiravir drug did not produce this result. “Similar results were obtained in other studies using low doses,” said Professor Delang. “High doses make a difference. It’s important to know that some clinical trials have already been set up to test favipiravir in humans.”

Careful optimism

Researchers are cautiously optimistic about favipiravir. “Because I took the drug just before exposing the hamster to the virus, I was able to prove that I could use the drug prophylactically, which helps prevent it,” says Sae Yamamoto Captain.

“If further studies show that the results are the same in humans, the drug can be used immediately after someone in the high-risk group comes into contact with the infected person. It may be effective even in the early stages of the disease. there is. .”

However, general prophylactic use is probably not an option, as it is unclear whether long-term use, especially at high doses, will have side effects.

No panacea

Further studies need to determine if humans can tolerate high doses of favipiravir. “In hamsters, few side effects were detected,” says Delang. In the past, the drug has already been prescribed to Ebola patients in high doses, and Ebola patients seem to tolerate it well.

“Favipiravir is not a panacea,” researchers warn. Neither this flu drug nor any other drug has been specifically developed for the coronavirus. As a result, favipiravir’s potency should be considered moderate at best.

The study also emphasizes the importance of testing treatments for SARS-CoV-2 in vivo using small animals. “Our hamster model is ideal for identifying new or existing drugs that may be considered in clinical research,” explains Professor Johan Neyts. “In the early days of the pandemic, such a model was not yet available. At that time, the only option was to investigate in patients whether drugs such as hydroxychloroquine could help them. Testing the treatment of hamsters provides important information. Clinical trials of ineffective drugs can prevent valuable time and energy loss. “

Not all research models are equal

Kaptein, Rocha-Pereira, Delang, Neyts contributed to recent commentary Nature Communications They give additional context to the prevailing inconsistent message about (hydroxy) chloroquine. In the early days of the pandemic, several studies were set up to test these drugs in cell culture. The results suggested that they may have antiviral effects. As a result, clinical trials have been organized to test the drug in humans. However, cell culture was not the best substitute for the human body and had no definitive effect on humans.

In their commentary, the author describes some recent studies on human Organ-on-chips and other complex in vitro models, mice, hamsters, and non-human primates. Each of these studies shows that hydroxychloroquine and chloroquine do not have the efficacy suggested by studies in cell culture. Therefore, the authors conclude that these malaria drugs are very unlikely to be effective in humans as a treatment for COVID-19.