Virologists from the KU Leuven Rega Institute in Belgium have proven that a therapy with the anti-malaria drug hydroxychloroquine doesn’t restrict SARS-CoV-2 coronavirus replication in hamsters. A excessive dose of the anti-flu drug favipiravir, against this, has an antiviral impact within the hamsters. The group revealed their findings within 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: looking for a vaccine to forestall an infection, and testing current 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 research, the group 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 utilized 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 in the future 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 within the hamsters.
Hydroxychloroquine versus favipiravir
Remedy with hydroxychloroquine had no impression: the virus ranges didn’t lower and the hamsters have been nonetheless infectious. “Regardless of the shortage of clear proof in animal fashions or medical 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 using hydroxychloroquine as a therapy towards COVID-19.”
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 within the hamsters that acquired 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. People who had not acquired the drug all grew to become contaminated after having shared a cage with an contaminated hamster.
A low dose of the drug favipiravir didn’t have this consequence. “Different research that used a decrease dose had related outcomes,” Professor Delang notes. “The excessive dose is what makes the distinction. That is vital to know, as a result of a number of medical trials have already been set as much as take a look at 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 might set up that the drugs will also be used prophylactically, so in prevention,” Suzanne Kaptein notes.
“If additional analysis reveals that the outcomes are the identical in people, the drug might be used proper after somebody from a high-risk group has come into contact with an contaminated particular person. It might seemingly even be energetic in the course of the early phases of the illness.”
Basic preventive use might be not an choice, nevertheless, as a result of it isn’t recognized whether or not long-term use, particularly at a excessive dose, has uncomfortable side effects.
Additional analysis should decide whether or not people can tolerate a excessive dose of favipiravir. “Within the hamsters, we detected hardly any uncomfortable side effects,” says Delang. Previously, the drug has already been prescribed in excessive doses to Ebola sufferers, who seem to have tolerated it effectively.
“Favipiravir shouldn’t be a panacea,” the researchers warn. This flu drug, nor another drug, has not been particularly developed towards coronaviruses. Because of this, the efficiency of favipiravir is to be thought of reasonable at greatest.
The research 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 current medication could also be thought of for medical research,” explains Professor Johan Neyts. “Within the early days of the pandemic, such a mannequin was not but out there. At the moment, the one choice was to discover in sufferers whether or not or not a drug equivalent to hydroxychloroquine might assist them. Nevertheless, testing remedies on hamsters gives essential data that may stop the lack of beneficial time and power with medical trials on medication that do not work.”
Not all analysis fashions are equal
Kaptein, Rocha-Pereira, Delang and Neyts just lately contributed to a commentary in Nature Communications through which they offer extra context to the contradictory messages which have been circulating about (hydroxy)chloroquine. Within the early days of the pandemic, a number of research have been set as much as take a look at these medication in cell cultures. The outcomes advised that they might have an antiviral impact. Because of this, medical trials have been organised to check the medication on people. Nevertheless, cell cultures will not be the perfect proxy for the human physique, and no conclusive impact was present in people.
Of their commentary, the authors describe a number of current research on human organ-on-chip and different advanced in vitro fashions, mice, hamsters, and non-human primates. Every of those research demonstrates that hydroxychloroquine and chloroquine would not have the efficacy advised by the research in cell cultures. Due to this fact, the authors conclude that these malaria medication are impossible to be efficient in people as a COVID-19 therapy.
The research “Favipiravir at excessive doses has potent antiviral exercise in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks exercise” by Suzanne Kaptein, Johan Neyts, Joana Rocha-Pereira, Leen Delang et al. was revealed in PNAS.
The commentary “Rising preclinical proof doesn’t assist broad use of hydroxychloroquine in COVID-19 sufferers” by Funnell et al. was revealed in Nature Communications (open entry).