Favipiravir has weak effect on SARS-CoV-2 and Hydroxychloroquine none at all in hamster model

By Dr. Ananya Mandal, MDJun 22 2020

A new study from Belgian researchers shows that antiviral drug Favipiravir could have a weak effect against the dreaded novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as seen in hamster models. However, the study also finds there is no efficacy of the much-touted drug Hydroxychloroquine.

The study titled, “Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine,” was published as a pre-peer review paper on the server bioRxiv*.

Novel Coronavirus SARS-CoV-2 This transmission electron microscope image shows SARS-CoV-2—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like.Image captured and colorized at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

COVID-19 and drug treatment

The COVID-19 pandemic caused by the SARS-CoV-2 was first reported in Wuhan China in December 2019. Since then, it has infected a large population around the world in almost all countries. Nearly half a million people have died of the infection, and there are no treatment options and no effective vaccines that could prevent this infection. There is a desperate need for effective antiviral drugs. Several existing drugs such as Hydroxychloroquine and Chloroquine (for SLE and malaria respectively), Remdesivir (for Ebola), Favipiravir (for influenza), Tocilizumab, Ivermectin (antiparasitic), Azithromycin (antibacterial macrolide antibiotic), etc. are thus repurposed for use against this virus. The most challenging aspect of proving if any of these drugs actually work against SARS CoV-2 is the lack of small animal models or in vitro testing models on which they could be tested before trying them on humans.

What was this study about?

The main focus of tackling this pandemic write the researchers are “repurposing of drugs that have been approved for other diseases.” They explain that these repurposed drugs are most likely to be not highly effective against SARS-CoV-2. Some of these, however, have been found to inhibit the virus in cell cultures.

This study focussed on two such drugs - Hydroxychloroquine and favipiravir. They wrote that Hydroxychloroquine is known to inhibit several viruses such as coronaviruses (SARS-CoV-1, MERS-CoV). Similarly, Favipiravir is a broad-spectrum antiviral drug that was approved in Japan in 2014 for influenza.

There have been studies with Vero E6 cells (cell cultures) on which these drugs were found to be effective against the SARS CoV-2.

The team wrote that studies have shown that favipiravir “acts as a nucleotide analog via a combination of chain termination, slowed viral RNA synthesis, and lethal mutagenesis.” They also added, “Despite the lack of clear evidence, HCQ is currently widely used for the treatment of COVID-19, often in combination with a second-generation macrolide such as azithromycin.”

What was done in this study?

For this study, the team used a small animal model in Syrian hamsters. They evaluated the antiviral activity of small molecules on the infection as well as the transmission of the infection. In the animals, the virus was introduced intranasally or via the nose. The virus sample used to infect the hamsters was the SARS CoV-2 strain called the “BetaCov/Belgium/GHB-03021/2020 (EPI ISL 407976|2020-02-03)”, which was collected from the nasopharyngeal swab from an asymptomatic patient who had returned from Wuhan, China at the start of February 2020. The sample was obtained from an RT-qPCR sample.

Thereafter the levels of the virus were found to be raised to high titers in the lungs of the animals. They also developed pathology, which was similar to humans when they developed mild COVID-19 infection. The drugs favipiravir or Hydroxychloroquine (with and without azithromycin) were administered to the infected hamsters and the effects of the drugs were noted.

What was found?

The study animals underwent a micro-CT scan to analyze the effects of the virus on their lungs and the effects of the drugs on the infection progression. The lung tissues of the treated and non treated hamsters were also collected, and histopathology was performed. Results showed that there were no additional benefits or improvements seen with therapy compared to untreated hamsters.

They wrote, “In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments.”

The pharmacokinetic patterns of the drugs were also studied, and it was noted that low lung exposure of Hydroxychloroquine was not the main reason why it was not effective.

Doesn’t work and doesn’t work

The researchers wrote in conclusion, “we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds.” This study can be critical in future drug development because it could help pre-clinical studies of new drugs against the SARS CoV-2 virus.

In trialing the two repurposed drugs Favipiravir and Hydroxychloroquine, the team found that Hydroxychloroquine either alone or combined with azithromycin was not effective against preventing COVID-19 infection or treating the infection. They wrote that from earlier studies on ferrets and macaques, it is evident that there is “no scientific basis for further use of the drug in humans.” The role of favipiravir is also not very pronounced, they concluded.

The authors wrote, “The very modest reduction of viral load in the lungs of hamsters treated with favipiravir and the lack of efficacy in the transmission model, also suggests that the potential benefit of this drug in humans may be limited as well.”

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources