Lab service technicians need to use protective matches when dealing with contagious SARS-CoV-2 samples. Credit: Layla Aerts – KU Leuven
Virologists at the Rega Institute have actually revealed that the anti-malaria drug hydroxychloroquine does not limitation SARS-CoV-2 coronavirus duplication in hamsters. A high dosage of the anti-flu drug favipiravir, by contrast, has an antiviral impact in the hamsters. The group released their findings in the Proceedings of the National Academy of Sciences (PNAS).
Virologists at the KU Leuven Rega Institute have actually been dealing with 2 lines of SARS-CoV-2 research study: looking for a vaccine to avoid infection, and screening existing drugs to see which one can lower the quantity of infection in contaminated individuals.
To test the effectiveness of the vaccine and antivirals preclinically, the scientists utilize hamsters. The rodents are especially appropriate for SARS-CoV-2 research study since the infection duplicates itself highly in hamsters after infection. Moreover, hamsters establish a lung pathology comparable to moderate COVID-19 in human beings. This is not the case with mice, for instance.
For this research study, the group of Suzanne Kaptein (PhD), Joana Rocha-Pereira (PhD), Professor Leen Delang, and Professor Johan Neyts offered the hamsters either hydroxychloroquine or favipiravir – a broad-spectrum antiviral substance abuse in Japan to deal with influenza – for 4 to 5 days. They checked a number of dosages of favipiravir. The hamsters were contaminated with the SARS-CoV-2 infection in 2 methods: by placing a high dosage of infection straight into their noses or by putting a healthy hamster in a cage with a contaminated hamster. Drug treatment was begun one hour prior to the direct infection or one day prior to the direct exposure to a contaminated hamster. Four days after infection or direct exposure, the scientists determined just how much of the infection existed in the hamsters.
Hydroxychloroquine versus favipiravir
Treatment with hydroxychloroquine had no effect: the infection levels did not reduce and the hamsters were still contagious. “Despite the lack of clear evidence in animal models or clinical studies, many COVID-19 patients have already been treated with hydroxychloroquine,” discusses Joana Rocha-Pereira. “Based on these results and the results of other teams, we advise against further exploring the use of hydroxychloroquine as a treatment against COVID-19.”
Hamsters are especially appropriate for SARS-CoV-2 research study. Credit: © Layla Aerts – KU Leuven
A high dosage of favipiravir, nevertheless, had a powerful impact. A couple of days after the infection, the virologists identified barely any contagious infection particles in the hamsters that got this dosage which had actually been contaminated intranasally. Moreover, hamsters that remained in a cage with a contaminated hamster and had actually been provided the drug did not establish an apparent infection. Those that had actually not gotten the drug all ended up being contaminated after having actually shared a cage with a contaminated hamster.
A low dosage of the drug favipiravir did not have this result. “Other studies that used a lower dose had similar results,” Professor Delang notes. “The high dose is what makes the difference. That’s important to know because several clinical trials have already been set up to test favipiravir on humans.”
Cautious optimism
The scientists are very carefully positive about favipiravir. “Because we administered the drug shortly before exposing the hamsters to the virus, we could establish that the medicine can also be used prophylactically, so in prevention,” Suzanne Kaptein notes.
Lab service technicians at work. Credit: © Layla Aerts – KU Leuven
“If further research shows that the results are the same in humans, the drug could be used right after someone from a high-risk group has come into contact with an infected person. It may likely also be active during the early stages of the disease.”
General preventive usage is most likely not an alternative, nevertheless, since it is not understood whether long-lasting usage, specifically at a high dosage, has negative effects.
No remedy
Further research study will need to identify whether human beings can endure a high dosage of favipiravir. “In the hamsters, we detected hardly any side effects,” states Delang. In the past, the drug has actually currently been recommended in high dosages to Ebola clients, who appear to have actually endured it well.
“Favipiravir is not a panacea,” the scientists caution. This influenza drug, nor any other drug, has actually not been particularly established versus coronaviruses. As an outcome, the effectiveness of favipiravir is to be thought about moderate at finest.
The research study likewise highlights the significance of utilizing little animals to evaluate treatments versus SARS-CoV-2 in vivo. “Our hamster model is ideally suited to identify which new or existing drugs may be considered for clinical studies,” discusses 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 explore in patients whether or not a drug such as hydroxychloroquine could help them. However, testing treatments on hamsters provides crucial information that can prevent the loss of valuable time and energy with clinical trials on drugs that don’t work.”
Reference: “Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity” by Suzanne J. F. Kaptein, Sofie Jacobs, Lana Langendries, Laura Seldeslachts, Sebastiaan ter Horst, Laurens Liesenborghs, Bart Hens, Valentijn Vergote, Elisabeth Heylen, Karine Barthelemy, Elke Maas, Carolien De Keyzer, Lindsey Bervoets, Jasper Rymenants, Tina Van Buyten, Xin Zhang, Rana Abdelnabi, Juanita Pang, Rachel Williams, Hendrik Jan Thibaut, Kai Dallmeier, Robbert Boudewijns, Jens Wouters, Patrick Augustijns, Nick Verougstraete, Christopher Cawthorne, Judith Breuer, Caroline Solas, Birgit Weynand, Pieter Annaert, Isabel Spriet, Greetje Vande Velde, Johan Neyts, Joana Rocha-Pereira and Leen Delang, 9 October 2020, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2014441117
