An anti-parasitic drug that is available around the world stops SARS-CoV-2 coronavirus from replicating in cells within a couple of days, according to findings from in vitro studies by Monash University’s Biomedicine Discovery Institute (BDI), working with the Peter Doherty Institute of Infection and Immunity.
BDI research lead Kylie Wagstaff, PhD, said the studies showed that the drug, ivermectin, started to become effective against SARS-CoV-2 in lab-grown cells within just a day. “We found that even a single dose could essentially remove all viral RNA by 48 hours and that even at 24 hours there was a really significant reduction in it,” Wagstaff commented. The researchers’ report is available as a pre-proof paper in Antiviral Research, titled, “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.”
Ivermectin is approved by the FDA for treating a number of parasitic infections, and the drug has an established safety profile, the authors wrote. Studies have suggested that ivermectin may also be effective in vitro against a broad range of viruses, including HIV, Dengue, influenza, and Zika virus. Wagstaff made a previous breakthrough finding on ivermectin in 2012, when, in collaboration with BDI co-author David Jans, PhD, she identified antiviral activity of ivermectin. Jans and his team have been researching the antiviral effects of ivermectin for more than 10 years.
“Ivermectin is an FDA-approved broad-spectrum antiparasitic agent that in recent years we, along with other groups, have shown to have antiviral activity against a broad range of viruses in vitro,” the authors stated. It was initially found that the drug inhibited the interaction between the HIV-integrase protein (IN) and the importin (IMP) α/ß1 heterodimer, which is responsible for IN nuclear import, the authors explained. Beyond HIV inhibition, the antiviral effects of ivermectin have since been found against other RNA viruses, potentially through the same mechanism. “Importantly, it has been demonstrated to limit infection by RNA viruses such as DENV 1-4, West Nile Virus, Venezuelan equine encephalitis virus (VEEV), and influenza, with this broad-spectrum activity believed to be due to the reliance by many different RNA viruses on IMPα/ß1 during infection,” the team noted.
Multiple previous studies have separately indicated a potential role for IMPα/ß1 during infection with SARS-CoV-2, which is also an RNA virus, indicating that ivermectin may have anti-coronavirus activity. “Taken together, these reports suggested that ivermectin’s nuclear transport inhibitory activity may be effective against SARS-CoV-2,” the team stated.
Wagstaff and Jans started investigating whether ivermectin may work against the SARS-CoV-2 virus as soon as the pandemic identified. The researchers now report on their in vitro experiments with ivermectin against SARS-CoV-2-infected cells in the laboratory. The researchers said that the collective results in the system that they used “… demonstrate that ivermectin has antiviral action against the SARS-CoV-2 clinical isolate in vitro, with a single dose able to control viral replication within 24–48 h …”. And although the mechanism by which ivermectin works against the virus is not known, Wagstaff suggested it is likely that, based on its action in other viruses, the drug acts to stop the virus dampening down the host cells’ ability to clear it. “We hypothesize that this is likely through inhibiting IMPα/ß1 mediated nuclear import of viral proteins, as shown for other RNA viruses; confirmation of this mechanism in the case of SARS-CoV-2, and identification of the specific SARS-CoV-2 and/or host component(s) impacted is an important focus future work in this laboratory,” the investigators wrote. They plan to continue their studies to confirm their findings and define the antiviral mechanism of action.
The scientists suggested that an effective antiviral against SARS-CoV-2, if given to patients during early infection, could help to limit viral load, prevent progression to severe disease, and limit transmission between people. “Benchmarking testing of ivermectin against other potential antivirals for SARS-Cov-2 with alternative mechanisms of action would thus be important as soon as practicable,” they stated.
It will also be critical to test different doses of ivermectin that mimic current approved usage in humans. “Ivermectin is very widely used and seen as a safe drug. We need to figure out now whether the dosage you can use it at in humans will be effective—that’s the next step,” Wagstaff said. The team noted that recent reviews and a meta-analysis have indicated that high-dose ivermectin has a comparable safety profile to that of standard low-dose treatment, although there isn’t yet enough evidence to make conclusions about the safety profile in pregnancy.
“As the virologist who was part of the team who were first to isolate and share SARS-CoV-2 outside of China in January 2020, I am excited about the prospect of ivermectin being used as a potential drug against COVID-19,” commented lead author Leon Caly, PhD, who is Royal Melbourne Hospital’s senior medical scientist at the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute, where experiments with SARS-CoV-2 were conducted.
“In times when we’re having a global pandemic and there isn’t an approved treatment, if we had a compound that was already available around the world then that might help people sooner,” added Wagstaff. “Realistically it’s going to be a while before a vaccine is broadly available.” Acknowledging that the use of ivermectin to combat COVID-19 would depend on the results of further preclinical testing and ultimately clinical trials, Wagstaff said funding is now urgently required to keep progressing the work.