A group of scientists in Germany have identified a drug called camostat mesylate, that they believe may work to combat COVID-19, the disease caused by the SARS-CoV-2 coronavirus.

The new study published last week in Cell,
shows that SARS-CoV-2 binds to human cells in a similar way to the
original SARS coronavirus (SARS-CoV) that caused a worldwide outbreak in
2003, with this binding depending on viral proteins called ‘spike’
proteins.

“Spike is so named because that’s what it looks like: a spike on the
surface of the virus particle,” said Angela L. Rasmussen, PhD, a
virologist in the faculty of the Center for Infection and Immunity at
the Columbia Mailman School of Public Health. “In order for a virus to
infect a cell, it has to attach itself to a protein on the surface of
that cell which we call the receptor. For SARS-CoV-2, this is a protein
called ACE2. Spike binds ACE2 and allows SARS-CoV-2 to enter and infect
cells,” she added.

As well as this initial process, the spike protein has to be primed
by an enzyme called a protease in order for the virus to complete entry
into the cell. The study showed that similar to SARS-CoV, SARS-CoV-2
uses a protease called TMPRSS2 to complete this process.

The scientists then looked at whether there were any compounds
available that could stop the entry of coronavirus into the cell by
stopping the TMPRSS2 protease from working. From previous work on
SARS-CoV, they found one potential candidate called camostat mesylate
and showed that the drug stopped SARS-CoV-2 from infecting lung cells in
a dish.

“We found that SARS-CoV-2, like SARS-CoV, uses the host proteins ACE2
and TMPRSS2 to enter cells. Both viruses should therefore infect
similar cells in patients and may cause disease via similar mechanisms,”
said Markus Hoffmann, PhD, researcher in the Infection Biology Unit of
the German Primate Center, Leibniz Institute for Primate Research,
Göttingen, Germany and first author of the paper.

Developing new drugs for infectious diseases or even diseases such as
cancer or neurological conditions can take years, even decades. But
camostat mesylate has already been tested in people, albeit not for the
treatment of COVID-19.

“We knew from our previous work that camostat mesylate was active
against other coronaviruses, including SARS-CoV. Therefore, we tested
whether it is also active against SARS-CoV-2,” said Stefan Pöhlmann,
PhD, Professor in the same institute in Göttingen. “Our study shows that
camostat mesylate blocks infection of cells with SARS-CoV-2-like
particles and with authentic, patient-derived SARS-CoV-2. Moreover,
camostat mesylate inhibited infection of important target cells – human
lung epithelial cells,” he added.

The compound is approved in Japan
for the treatment of a number of non-infectious conditions in people,
such as chronic pancreatitis and postoperative reflux esophagitis and
has also had some tests in mice infected with SARS-CoV. However, it has never been tested in humans with COVID-19.

“It does require trials in humans to determine if it’s effective, and
I suspect it would also require pre-clinical animal work with
SARS-CoV-2 specifically before human trials could start. If it has been
shown to be safe for clinical use in other countries, it may be
fast-tracked for FDA approval or the FDA may authorize emergency
off-label use,” said Rasmussen, indicating that the FDA will have to
examine safety data and pre-clinical data before determining which, if
any course of action to take with investigating the drug further.

One concern is that TMPRSS2 might not be the only protease that
controls spike priming and hence blocking it may be ineffective in
people as other proteases may act as backups, still allowing the virus
entry into cells. There are also questions to be asked about how the
drug would actually alter the ability of the virus to cause disease in
people.

“Pathogenesis can’t be studied in cultured cells, so these questions
will need to be addressed using animal models and human clinical
samples,” said Rasmussen.

Given the similarities between SARS-CoV and the current virus
SARS-CoV-2, the researchers also looked at whether people who recovered
from SARS had any immunity to the new virus strain. They took serum
containing antibodies taken from 3 recovering SARS-CoV patients, frozen
back around the time of the original outbreak in 2003 and showed that
this blocked entry of SARS-CoV-2 into cells.

“Antibodies from patients who had recovered from SARS blocked the
SARS-CoV-2 from infecting cells in culture. This suggests that
antibodies against SARS might be useful as a treatment for SARS-CoV-2,”
said Rasmussen.

SARS in 2003 was a smaller outbreak compared to the current situation with only 8,098 cases formally recorded
and over 7,000 people surviving. It is not known how many of these
people are still alive today, but it is possible that they will have
some immunity to COVID-19. On a wider scale, studying these people may
provide incredibly useful clues about successfully treating COVID-19.
So, what are the next steps for the researchers?

“We are currently analyzing whether camostat mesylate-related
inhibitors show improved antiviral activity. So far we have not been
contacted by others regarding off-label use of camostat mesylate.
However, we are contacting physicians to discuss this option,” said
Pöhlmann.

There are currently no FDA-approved treatments for COVID-19, but last
week, the National Institutes of Health announced that the antiviral
drug remdesivir had begun testing in a human clinical trial in the U.S. Remdesivir, marketed by Gilead Sciences has previously shown promise in preventing MERS coronavirus disease in tests on monkeys and is already being used in human trials in Wuhan.
The first patient in the U.S. is an American who was evacuated from the
Diamond Princess cruise ship, which became a floating incubator for the
virus, resulting in over 700 infections and six deaths reported so far.