Many in the antiviral field, including myself, have questioned the validity of both, and in fact, one of the articles was subsequently decried by the scientific society and the editor of the journal which has it. published.
Since then, HQC has had a bumpy ride. It was originally approved by the FDA for emergency use. The FDA then quickly reversed its decision when numerous reports of deaths from cardiac arrhythmias emerged. This news put an end to many clinical trials.
Either way, some scientists have continued to study it in hopes of finding a cure for this deadly virus.
How the job was done
The new study was conducted by German scientists who tested HQC on a collection of different types of cells to understand why this drug does not stop the virus from infecting humans.
Their results clearly show that HQC can prevent the coronavirus from infecting kidney cells of the African green monkey. But it does not inhibit the virus in human lung cells – the main site of infection for the SARS-CoV-2 virus.
For the virus to enter a cell, it can do so through two mechanisms – one, when the SARS-CoV-2 spike protein attaches to the ACE2 receptor and inserts its genetic material into the cell. In the second mechanism, the virus is absorbed into certain special compartments of cells called endosomes.
Depending on the type of cell, some, such as kidney cells, need an enzyme called cathepsin L for the virus to successfully infect them. In lung cells, however, an enzyme called TMPRSS2 (on the cell surface) is needed. Cathepsin L requires an acidic environment to function and allow the virus to infect the cell, unlike TMPRSS2.
In green monkey kidney cells, hydroxychloroquine and chloroquine decrease acidity, which deactivates the cathepsin L enzyme, preventing the virus from infecting monkey cells. In human lung cells, which have very low levels of the cathepsin L enzyme, the virus uses the TMPRSS2 enzyme to enter the cell.
But since this enzyme is not controlled by acidity, neither HCQ nor CQ can stop SARS-CoV-2 from infecting the lungs or stop the virus from replicating.
Why is this important
This matters for several reasons. First, a lot of time and money has been spent studying a drug that many scientists believe is not effective in killing the virus.
The second reason is that the studies that reported antiviral activity of hydroxychloroquine did not involve lung epithelial cells. Thus, their results are not relevant to properly study SARS-CoV-2 infections in humans.
As scientists continue to research new drugs and attempt to reuse old ones, such as hydroxychloroquine, it is essential that researchers take the time to think about their study design.
In short, those of us involved in the development of antiviral drugs should all learn a lesson from this study. It is important not only to focus our efforts on finding drugs that will directly stop viral replication, but also to study the virus at the primary site of infection.
Katherine Seley-Radtke, professor of chemistry and biochemistry and president-elect of the International Society for Antiviral Research, University of Maryland, Baltimore County.
This article is republished from The Conversation under a Creative Commons license. Read the original article.