Draft 1

Science Popularization Draft 1: New Oral Drug for COVID-19 Shows Promise in

Preventing Severe Disease

The COVID-19 pandemic has caused over 5 million deaths and over 235 million

infections, globally. While we now have, for the most part, widespread access to

vaccination against the SARS-CoV-2 virus, better known as COVID-19 or Coronavirus,

we are yet to have an effective, FDA-approved drug to actually treat the virus once

infected. To tackle this challenge, scientists at Pfizer have now targeted a main

SARs-CoV-2 protease (SARS-CoV-2 Mpro) inhibitor that they found to have significant

antiviral activity in humans, as well as proper selectivity and safety profiles.

A protease inhibitor is a class of drug that works by blocking, or “inhibiting,” the

reproduction of certain cells and viruses. It does this by disabling the enzymes that aid

in the replication process. This SARs-CoV-2 protease inhibitor thus acts by preventing

the virus from replicating in your body.

The researchers focused on this class of drug specifically because of its

resistance to new variants of the virus. While some drugs target the so-called “spike

protein” of the virus (the part of the virus that attaches to human cells), this can result in

degrading of efficacy over time as the structure of this protein continues to mutate more

and more with each new variant. However, a protease inhibitor does not target this area

of the virus specifically, which means that it should continue to be effective as the virus

mutates.
 Scientists Owen and colleagues first needed to identify the SARS-CoV-2 Mpro

inhibitor that would best target the virus. In order to do this, they studied 6 different

inhibitors and found the most potent to be the PF-00835231 inhibitor, which they then

used for the rest of their study.

After the identification of the most effective inhibitor, Owen and colleagues went

on to perform experiments where they tested the efficacy of the inhibitor in live mice.

They first infected cohorts of six mice with the SARS-CoV-2 virus. They then tracked

body weight, virus titer (a measurement of the virus’ ability to infect host cells) in the

lungs, concentrations of the virus in the blood plasma, and post-euthanasia health of

lung tissue. They found that with both doses of 300 and 1000 mg of the inhibitor per 1

kg of body weight resulted in significantly less weight loss, lung virus titer, and

concentration of the virus in the plasma, as well as significantly healthier lung tissue

when compared to mice that were not treated with the drug.

Since the drug had such promising results in mice experiments, the researchers

were then able to begin pre-clinical testing with human subjects. This trial consisted of

about 1200 volunteers. Once again, both doses (300 and 1000 mg/kg) showed a

decrease in concentration of the virus in the plasma of the participants’ blood.

Considering these promising results, this SARS-CoV-2 protease inhibitor drug

could be on its way to FDA approval soon. This could mark a large leap in the

availability and effectiveness of treatment against COVID-19.

Draft 2

Science Popularization Draft 2: New Oral Drug for COVID-19 Shows Promise in

Preventing Severe Disease

 The COVID-19 pandemic has caused over 5 million deaths and over 235 million

infections globally. That being said, the United States now has, for the most part,

widespread access to vaccination against the SARS-CoV-2 virus, better known as

COVID-19 or Coronavirus. However, we are yet to have an effective, FDA-approved

drug to actually treat the virus once infected. To tackle this challenge, scientists at Pfizer

have now targeted a main SARS-CoV-2 protease (SARS-CoV-2 Mpro) inhibitor that they

found to have significant antiviral activity in humans, as well as proper selectivity and

safety profiles.

A protease inhibitor is a class of drug that works by blocking, or “inhibiting,” the

reproduction of certain cells and viruses. It does this by disabling the enzymes that aid

in the replication process. This SARS-CoV-2 protease inhibitor thus acts by preventing

the virus from replicating in your body.

The researchers focused on this class of drug specifically because of its

resistance to new variants of the virus. While some drugs target the so-called “spike

protein” of the virus (the part of the virus that attaches to human cells), this can result in

degrading effectiveness over time as the structure of this protein continues to mutate

more and more with each new variant. However, a protease inhibitor does not target this

area of the virus specifically, which means that it should continue to be effective as the

virus mutates.

Scientists Owen and colleagues first needed to identify the SARS-CoV-2 Mpro

inhibitor that would best target the virus. In order to do this, they studied 6 different
inhibitors and found the most potent to be the PF-00835231 inhibitor, which they then

used for the rest of their study.

After the identification of the most effective inhibitor, Owen and colleagues went

on to perform experiments where they tested how effective this inhibitor is in actual live

mice. They first infected groups of six mice with the SARS-CoV-2 virus. Then, they

tracked body weight, lung virus titer (a measurement of the virus’ ability to infect host

cells), concentrations of the virus in the blood plasma, and post-euthanasia health of

lung tissue. They found that both doses of 300 mg and 1000 mg of the inhibitor per 1 kg

of body weight (mg/kg) resulted in significantly less weight loss, lung virus titer, and

concentration of the virus in the plasma, as well as significantly healthier lung tissue

when compared to mice that were not treated with the drug.

Since the drug had such promising results in mice experiments, the researchers

were then able to begin pre-clinical testing with human subjects. Once again, both

doses (300 mg/kg and 1000 mg/kg) showed a decrease in concentration of the virus in

the plasma of the participants’ blood.

Considering these exciting and encouraging data, this SARS-CoV-2 protease

inhibitor drug could be on its way to FDA approval soon. This could be a game-changer

for prevention of severe disease and so-called “long-Covid,” where some symptoms–

particularly fatigue, loss of taste and smell, and lingering respiratory effects– continue to

impact people long after they have “recovered” from the virus. Ultimately, this could

mark a large leap in the availability and effectiveness of treatment against COVID-19.

References
Owen, Dafydd R., et al. “An Oral SARS-COV-2 m PRO Inhibitor Clinical Candidate for

the Treatment of COVID-19.” Science, vol. 374, no. 6575, 2021, pp. 1586–1593.,

https://doi.org/10.1126/science.abl4784.

Final Draft

Science Popularization Final Draft: New Oral Drug for COVID-19 Shows Promise

in Preventing Severe Disease

The COVID-19 pandemic has caused over 5 million deaths and 235 million

infections globally. Fortunately, the United States now has widespread access to

vaccination against the SARS-CoV-2 virus, better known as the coronavirus that causes

COVID-19. However, we are yet to have an effective and easy-to-take FDA-approved

drug to actually treat the virus once infected. To tackle this challenge, scientists at Pfizer

have now created a new oral drug that they found to have significant antiviral activity in

humans, and in preliminary tests, appears to be safe.

The new drug is a protease inhibitor, which is a class of drug that works by

blocking, or “inhibiting,” the reproduction of certain cells and viruses. It does this by

disabling the enzymes (proteins that speed up reactions in the body) that aid in the

replication process. This SARS-CoV-2 protease inhibitor acts by preventing the virus

from replicating in the body.

The researchers focused specifically on this class of drug because it works not

only on the original virus, but on new variants of the virus, such as Delta and Omicron.

While some drugs target the so-called “spike protein” of the virus (the part of the virus
that attaches to human cells), these can reduce in effectiveness over time as the

structure of this protein continues to mutate more and more with each new variant.

However, a protease inhibitor does not target this area of the virus specifically, which

means that it should continue to be effective as the virus mutates.

The Pfizer researchers first needed to identify the protease inhibitor that would

best target the virus. To do this, they studied six different inhibitors and found the most

potent and easy to synthesize to be the PF-07321332 inhibitor–named after its chemical

composition–which they then used for the rest of their study.

After the identification of the most effective inhibitor, Owen and the rest of the

Pfizer team went on to perform experiments where they tested how effective this

inhibitor is in actual live mice. They first infected groups of six mice with a SARS-CoV-2

virus that was specifically engineered to infect them. Then, after treating some of them

with the new drug, they tracked body weight, lung virus titer (a measurement of the

virus’ ability to infect host cells in the lungs), and concentrations of the virus in the blood

plasma. After killing the mice, they also assessed the health of lung tissue. They found

that both doses of the inhibitor tested resulted in significantly less weight loss, lung virus

titer, and concentration of the virus in the plasma. They also saw significantly healthier

lung tissue when compared to mice that were not treated with the drug.

Since the drug had such promising results in mice experiments, the researchers

were later able to begin pre-clinical testing with human subjects. This next Pfizer study

encompassed phase ⅔ for the clinical trials. It consisted of about 1200 volunteers.

Further, since Pfizer is now requesting official approval for the drug, they gave it a brand

name: PAXLOVID.
 The results of the clinical trials were similarly promising. They found an 89%

decrease in risk of hospitalization and death when comparing subjects who took

PAXLOVID and subjects who received a placebo. Additionally, as of day 28 of the trial,

subjects who took the drug reported no deaths, while subjects who took a placebo

reported 10 deaths.

Considering these exciting and encouraging data, this SARS-CoV-2 protease

inhibitor drug, PAXLOVID, could be on its way to FDA approval soon. This is potentially

a game-changer for those already infected with COVID-19, particularly those who are

more vulnerable to severe disease. Moreover, an orally administered drug offers faster

and easier treatment compared to i.v. options, which require hospitalization. Especially

considering that hospitals have been pushed past capacity for large periods of the

pandemic. Ultimately, this could mark a large leap in the availability and effectiveness of

treatment against COVID-19.