Hydroxychloroquine Does Not Counter SARS-CoV-2 (COVID-19 Virus) in Hamsters, but Favipiravir Does

Lab technicians should put on protecting fits when working with infectious SARS-CoV-2 samples. Credit score: Layla Aerts – KU Leuven

Virologists on the Rega Institute have proven that the anti-malaria drug hydroxychloroquine doesn’t restrict SARS-CoV-2 coronavirus replication in hamsters. A excessive dose of the anti-flu drug favipiravir, in contrast, has an antiviral impact in the hamsters. The workforce revealed their findings in the Proceedings of the Nationwide Academy of Sciences (PNAS).

Virologists on the KU Leuven Rega Institute have been engaged on two strains of SARS-CoV-2 analysis: trying to find a vaccine to forestall an infection, and testing present medication to see which one can cut back the quantity of virus in contaminated individuals. 

To check the efficacy of the vaccine and antivirals preclinically, the researchers use hamsters. The rodents are significantly appropriate for SARS-CoV-2 analysis as a result of the virus replicates itself strongly in hamsters after an infection. Furthermore, hamsters develop a lung pathology just like gentle COVID-19 in people. This isn’t the case with mice, for instance. 

For this examine, the workforce of Suzanne Kaptein (PhD), Joana Rocha-Pereira (PhD), Professor Leen Delang, and Professor Johan Neyts gave the hamsters both hydroxychloroquine or favipiravir – a broad-spectrum antiviral drug used in Japan to deal with influenza – for 4 to 5 days. They examined a number of doses of favipiravir. The hamsters have been contaminated with the SARS-CoV-2 virus in two methods: by inserting a excessive dose of virus immediately into their noses or by placing a wholesome hamster in a cage with an contaminated hamster. Drug therapy was began one hour earlier than the direct an infection or at some point earlier than the publicity to an contaminated hamster. 4 days after an infection or publicity, the researchers measured how a lot of the virus was current in the hamsters.

Remedy with hydroxychloroquine had no influence: the virus ranges didn’t lower and the hamsters have been nonetheless infectious. “Regardless of the shortage of clear proof in animal fashions or scientific research, many COVID-19 sufferers have already been handled with hydroxychloroquine,” explains Joana Rocha-Pereira. “Primarily based on these outcomes and the outcomes of different groups, we advise towards additional exploring the usage of hydroxychloroquine as a therapy towards COVID-19.”

Hamsters are significantly appropriate for SARS-CoV-2 analysis. Credit score: © Layla Aerts – KU Leuven

A excessive dose of favipiravir, nevertheless, had a potent impact. A number of days after the an infection, the virologists detected hardly any infectious virus particles in the hamsters that obtained this dose and that had been contaminated intranasally. Furthermore, hamsters that have been in a cage with an contaminated hamster and had been given the drug didn’t develop an apparent an infection. Those who had not obtained the drug all turned contaminated after having shared a cage with an contaminated hamster.

A low dose of the drug favipiravir didn’t have this end result. “Different research that used a decrease dose had related outcomes,” Professor Delang notes. “The excessive dose is what makes the distinction. That’s necessary to know as a result of a number of scientific trials have already been set as much as check favipiravir on people.”

The researchers are cautiously optimistic about favipiravir. “As a result of we administered the drug shortly earlier than exposing the hamsters to the virus, we may set up that the drugs will also be used prophylactically, so in prevention,” Suzanne Kaptein notes.

Lab technicians at work. Credit score: © Layla Aerts – KU Leuven

“If additional analysis reveals that the outcomes are the identical in people, the drug may very well be used proper after somebody from a high-risk group has come into contact with an contaminated individual. It could possible even be lively throughout the early levels of the illness.” 

Common preventive use might be not an choice, nevertheless, as a result of it’s not recognized whether or not long-term use, particularly at a excessive dose, has negative effects.    

Additional analysis should decide whether or not people can tolerate a excessive dose of favipiravir. “Within the hamsters, we detected hardly any negative effects,” says Delang. Prior to now, the drug has already been prescribed in excessive doses to Ebola sufferers, who seem to have tolerated it properly. 

“Favipiravir will not be a panacea,” the researchers warn. This flu drug, nor some other drug, has not been particularly developed towards coronaviruses. In consequence, the efficiency of favipiravir is to be thought of reasonable at finest.

The examine additionally highlights the significance of utilizing small animals to check therapies towards SARS-CoV-2 in vivo. “Our hamster mannequin is ideally suited to determine which new or present medication could also be thought of for scientific research,” explains Professor Johan Neyts. “Within the early days of the pandemic, such a mannequin was not but obtainable. At the moment, the one choice was to discover in sufferers whether or not or not a drug equivalent to hydroxychloroquine may assist them. Nevertheless, testing remedies on hamsters offers essential data that may forestall the lack of useful time and vitality with scientific trials on medication that don’t work.”

Reference: “Favipiravir at excessive doses has potent antiviral exercise in SARS-CoV-2−contaminated hamsters, whereas hydroxychloroquine lacks exercise” 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 Nationwide Academy of Sciences.
DOI: 10.1073/pnas.2014441117
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