Virologists from the KU Leuven Rega Institute in Belgium have proven that a remedy 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 staff 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: trying to find a vaccine to forestall an infection, and testing current medicine to see which one can cut back the quantity of virus in contaminated folks.
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 much like delicate COVID-19 in people. This isn’t the case with mice, for instance.
For this research, the staff 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 had 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 remedy was began one hour earlier than the direct an infection or someday 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 influence: the virus ranges didn’t lower and the hamsters had been nonetheless infectious. “Regardless of the dearth of clear proof in animal fashions or scientific research, many COVID-19 sufferers have already been handled with hydroxychloroquine,” explains Joana Rocha-Pereira. “Based mostly on these outcomes and the outcomes of different groups, we advise in opposition to additional exploring using hydroxychloroquine as a remedy in opposition to COVID-19.”
A excessive dose of favipiravir, nevertheless, had a potent impact. Just a few 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 had 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 end result. “Different research that used a decrease dose had comparable outcomes,” Professor Delang notes. “The excessive dose is what makes the distinction. That is necessary to know, as a result of a number of scientific 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 can 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 individual. It might probably even be lively throughout the early phases of the illness.”
Normal preventive use might be not an possibility, nevertheless, as a result of it isn’t identified 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 nicely.
“Favipiravir just isn’t a panacea,” the researchers warn. This flu drug, nor some other drug, has not been particularly developed in opposition to coronaviruses. In consequence, 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 in opposition to SARS-CoV-2 in vivo. “Our hamster mannequin is ideally suited to establish which new or current medicine 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 out there. At the moment, the one possibility was to discover in sufferers whether or not or not a drug similar to hydroxychloroquine might assist them. Nonetheless, testing remedies on hamsters gives essential info that may forestall the lack of worthwhile time and power with scientific trials on medicine that do not work.”
Not all analysis fashions are equal
Kaptein, Rocha-Pereira, Delang and Neyts lately contributed to a commentary in Nature Communications during which they offer further context to the contradictory messages which have been circulating about (hydroxy)chloroquine. Within the early days of the pandemic, a number of research had been set as much as take a look at these medicine in cell cultures. The outcomes prompt that they may have an antiviral impact. In consequence, scientific trials had been organised to check the medicine on people. Nonetheless, cell cultures should not one of the best 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 complicated in vitro fashions, mice, hamsters, and non-human primates. Every of those research demonstrates that hydroxychloroquine and chloroquine wouldn’t have the efficacy prompt by the research in cell cultures. Due to this fact, the authors conclude that these malaria medicine are not possible to be efficient in people as a COVID-19 remedy.
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).