Conversation: Covid19 Coronavirus-Pfizer is trying pills to defeat the virus

Although the focus has been primarily on vaccines, you may have heard that Pfizer is trying pills to treat Covid-19.

It sounds almost too good to be true. In fact, the results are very preliminary, but this is a promising approach.

Pfizer’s pill directly targets the virus itself, SARS-CoV-2, while most antiviral agents attempted to treat Covid-19 target the inflammatory and immune response caused by infection. ..

Strengthen protection against viruses

Many of the Covid-19-related illnesses are due to the violent inflammatory and immune responses that can occur in infections. The most successful treatments to date have targeted this enthusiastic immune response.

Inhaled corticosteroid budesonide, taken early in the disease, has been shown to reduce the incidence of more serious illnesses.

In people hospitalized with Covid-19 who need oxygen, the oral corticosteroid dexamethasone reduces the chance of death.

In the most severe cases — Covid patients admitted to the ICU — intravenously administered anti-inflammatory tocilizumab gives a person a better chance of survival.

However, these treatments do not target SARS-CoV-2 itself. Only the result of infection. Targeting the virus directly has proven to be more difficult.

Target SARS-CoV-2

Viruses like SARS-CoV-2 need to invade host cells in order to propagate. It attaches to cells using spike proteins (proteins on the surface of the virus) and then invades using the proteins of the cells themselves.

Once inside the cell, SARS-CoV-2 removes the exodermis and releases viral RNA (ribonucleic acid, a type of genetic material). It acts as a template, allowing the virus to replicate and infect other cells. At any point in this life cycle, the virus can be vulnerable to intervention.

SARS-CoV-2 has a 3C-like protease (3CLpro), an enzyme that plays an important role in the replication process. This protease is similar to the protease used by the SARS-CoV-1 (SARS) virus and is similar to the protease used by the Middle East Respiratory Virus (MERS).

Therefore, drugs that can effectively target 3CLpro and prevent viral replication may be beneficial against multiple known coronaviruses, and perhaps all future coronaviruses.

Protease inhibitors are used to treat other viral infections, especially chronic infections such as HIV and hepatitis C.

They were proposed early in the pandemic as possible treatments for Covid-19. However, the HIV drug lopinavir-ritonavir has been shown to be ineffective in two clinical trials, and drug levels may be too low to work against SARS-CoV-2. Higher doses may be effective, but they can also produce more side effects.

Scientists have also proposed a reusable antiviral drug, remdesivir, originally developed to treat Ebola. Remdesivir slows the virus’s ability to replicate RNA.

The first case report looked promising and saw the US Food and Drug Administration approve the drug for emergency use. However, the results of randomized controlled trials in critically ill Covid-19 inpatients were disappointing.

The duration of illness in the surviving patients was shortened, but it did not significantly reduce the likelihood of human death.

Of course, neither of these agents was specifically designed to target SARS-CoV-2. But in 2020, Pfizer / BioNtech identified a small molecule (PF-00835231) that blocks the SARS-CoV-2 3CLpro protease. Originally designed for SARS-CoV-1, the enzymes of the two viruses are almost the same.

PF-00835231 appears to reduce the replication of a series of coronaviruses, including SARS-CoV-2, in laboratory cells, alone or in combination with remdesivir. In addition, many animal models had reduced viral replication, which did not adversely affect safety. However, it is important to note that this study has not yet been peer-reviewed.

What now?

Pfizer / BioNTech is taking two drugs in a Covid-19 clinical trial: PF-07304814, intravenous injection for use in patients admitted with severe Covid-19, and PF-07321332, oral Agents, or pills. I’m sick. Both are formulations of 3CLpro inhibitors.

These Phase 1 trials, launched in March, represent the early stages of drug development. In these trials, healthy volunteers are selected and different doses of the drug are used to establish safety. They also examine whether the drug elicits a sufficient response in the body to show that the drug may be effective against SARS-CoV-2.

The next step is a Phase 2 or 3 trial to see if it improves Covid-19 results. This process usually takes years, but as the pandemic rages around the world, Pfizer says it will do so within a few months if Phase 1 testing is successful.

Applying antivirals in acute Covid-19 is difficult and rewarding. The results are preliminary at this stage, but these agents by Pfizer / BioNtech are promising. They can be used early in the disease, especially in people who are not well protected by vaccination or who are not vaccinated.

They can also be used as a precautionary measure to contain the outbreak of exposed people. They should be effective against all SARS-CoV-2 variants of concern, as well as other known and possibly emerging coronaviruses.

Pfizer’s recent suggestion that pills may be available by the end of the year is probably exaggerated. But the pandemic shows us what is possible in the realm of rapid scientific progress, and we look at this space with great interest.

•• Peter Walk, Co-professor of Medicine and Public Health, Newcastle University

•• This article will be republished from conversation Under a Creative Commons license. Please read the original article.