Last month, an announcement by Iran’s news agencies on the successful treatment of COVID-19 patients appears to have slipped beneath the radar. Unusually, contrary to customary reporting, the names of the drugs and the treatment were withheld. Has Iran found a possible cure for COVID-19? Dr James Freeman investigates.
For those of you who like executive summaries, here it is.
Iranian reports on success of clinical trials but details scanty
It may surprise you to know that doctors in Iran have commenced 109 clinical trials on treatments for COVID-19 and recently announced that
“Antiviral drugs have been successfully tested on critically ill patients with COVID-19 by the Infectious Diseases Department of Abadan University of Medical Science.”
The cure looks like no ICU deaths and rapid recovery for patients. While Iran has not announced the name of the drug, it can be accurately deduced via an analysis of their clinical trials database. The drug is a locally produced fixed dose combination of Sofosbuvir (Sovaldi) and Daclastasvir (Daklinza) which is normally used to treat Hepatitis C virus. In what I personally consider a staggering oversight, doctors in developed countries are not testing this combination. It has been right under our noses the whole time and we have left it to Iran to prove it works.
So, which are the possible anti-viral drugs used in the trials?
What follows gets a little technical for a moment then moves on to some Sherlock Holmes-style investigation and a call for action to duplicate the trials in Iran to see if their observations hold true.
Keeping in mind that both Hepatitis C (HCV) and SARS-CoV-2 are +ve sense RNA viruses (which means quite similar, in plain English) it would be reasonable to assume that nucleotide analogues (NUCs) proven to work for HCV might work on SARS-CoV-2. In simple terms, NUCs are fake letters in the RNA genetic alphabet CGAU.
Ribavirin, Remdesvir and Sofosbuvir are all NUCs and represent fake letters “G”, “A” and “U” respectively. The strategy of using fake genetic letters to impair the activity of critical viral polymerases (the thing that clones the genetic material) is well known and will not be discussed further.
With Hepatitis C, we can observe Ribavirin is weak with a log kill of only 0.5 (2/3 viruses killed) and a wide range of well-known side effects because it is not very selective. Conversely, Sofosbuvir is very potent with a log kill of 4.5 (31999/32000 viruses killed). Besides staggering potency, the key feature of Sofosbuvir is its lack of toxicity. Almost every other NUC developed for HCV, HIV and other viruses failed, not due to a lack of potency, but rather due to toxicity on human cells.
While there are high hopes for a Gilead drug called Remdesvir, the reality is that Remdesvir is intravenous only and currently only exists at experimental scale, so, even if it is proven to work, the likely global utility is small unless you are super rich.
Conversely, Sofosbuvir is a tablet and widely deployed making it a superior trials candidate on those grounds alone. We know Sofosbuvir is safe in humans, we know the doses, so why are we not testing it? We did, in fact, consider testing it way back in February but for reasons that elude me that avenue of investigation appears to simply evaporate.
Fortunately, some people are testing it in humans, and the results appear very encouraging.
