In a new study from Penn State, researchers found several FDA-approved drugs—including for type 2 diabetes, hepatitis C and HIV—strongly reduce the ability of the Delta variant of SARS-CoV-2 to replicate in human cells.
Specifically, they found that these drugs inhibit certain viral enzymes, called proteases, that are essential for SARS-CoV-2 replication in infected human cells.
The SARS-CoV-2 vaccines target the spike protein, but this protein is under strong selection pressure and, as we have seen with Omicron, can undergo significant mutations.
There remains an urgent need for SARS-CoV-2 therapeutic agents that target parts of the virus other than the spike protein that are not as likely to evolve.
Previous research has demonstrated that two SARS-CoV-2 enzymes—proteases including Mpro and PLpro—are promising targets for antiviral drug development.
Pfizer’s COVID-19 therapy Paxlovid, for example, targets Mpro. According to Jose, these enzymes are relatively stable; therefore, they are unlikely to develop drug-resistant mutations rapidly.
In the study, the team developed a new method to test 64 compounds, including inhibitors of HIV and hepatitis C proteases; cysteine proteases, which occur in certain protozoan parasites; and dipeptidyl peptidase, a human enzyme involved in type 2 diabetes.
From the 64 compounds, the team identified eleven that affected Mpro activity and five that affected PLpro activity.
Next, the team evaluated the antiviral activity of the 16 PLpro and Mpro inhibitors against SARS-CoV-2 viruses in live human cells.
They discovered that eight of them had dose-dependent antiviral activities against SARS-CoV-2.
In addition, the researchers found that treating cells with a combination of Mpro and PLpro inhibitors had an additive antiviral effect, providing even greater inhibition of SARS-CoV-2 replication.
Now the team is in the process of designing new compounds based on the structures they determined. They also plan to test the combination drugs that they already demonstrated to be effective in vitro in mice.
Although the scientists studied the Delta variant of SARS-CoV-2, they said the drugs will likely be effective against Omicron and future variants because they target parts of the virus that are unlikely to mutate significantly.
If you care about COVID, please read studies about new ways to predict who will get severe COVID-19 and die, and for people over 50, even ‘mild’ COVID 19 can cause dangerous health problems.
For more information about COVID, please see recent studies about low-cost drug that can treat COVID-19 effectively, and safely, and results showing that COVID booster shot can cut your death risk by 90%.
The study is published in Communications Biology and was conducted by Joyce Jose et al.
Copyright © 2022 Knowridge Science Report. All rights reserved.
