It usually takes years to develop safe and effective therapeutic agents for diseases. But the 199 pandemic requires immediate treatment because hundreds of millions of people have been infected and millions have died. Repurposing existing drugs that have been approved for another disease has the potential to deliver Covid-19 therapeutic agents faster.
The method was adopted by an inter-investigator agency team for Covid-19: Professor Gaetano Montelione, Dr. Khushboo Bafna, Dr. Balasubramanian Harish, Dr. Theresa Ramelot, Dr. Thomas Acton, and Catherine Royer Rensselear attslear Polytechnic Institute (RPI) (RPI) (RPI) (RPI) (RPI) ) (RPI); Professor Kris White, Professor Adolfo Garcia-Sastre, Dr. Romel Rosales, Dr. Lisa Miorin, Dr. Elena Moreno, and Thomas Kehrer, Icahn School of Medicine, Mount Sinai; Robert Kreu, University of Texas, Austin Professor Ge.
These researchers tested ten available hepatitis C virus (HCV) drugs to inhibit the replication capacity of SARS-COV-2, the virus that causes COVID-19, and showed how many of these HCV drugs are among them There is potential as a treatment for COVID-19. In particular, four of these HCV drugs enhance the antiviral activity of Remdesivir, the only antiviral drug to obtain Covid-19, up to 10 times. The study was published in the Journal Cell report.
Prof Montelione, the corresponding author of the paper, said: “Providing antiviral drugs that can be quickly deployed to fight the Covid-19-19 pandemic, we conducted this study to identify currently available drugs that have the potential to be reused. SARS-COV-2 virus that causes the 199 disease is an inhibitor.”
The motivation for this study was the observation that RPI researchers were seeing striking similarities between the structure of HCV proteases and one of the SARS-COV-2 proteases, known as the main protease. These viral proteases play an important role in viral infection. They wondered if existing drugs that bind to HCV protease and inhibit HCV protease may also bind to this SARS-COV-2 protease and inhibit it.
RPI researchers used supercomputers to model how drugs bind to viral proteins, predicting that ten HCV drugs can bind to the SARS-COV-2 protease. Furthermore, they showed that seven of these drugs inhibited the SARS-COV-2 protease
The Mount Sinai research team then tested the seven drugs in a safe biological culture facility to inhibit the ability of SARS-COV-2 virus to replicate in monkeys and cultures. All seven HCV drugs inhibit viral replication.
In subsequent experiments, the researchers were surprised to find that four HCV drugs (Simeprevir, vaniprevir, paritaprevir and Grazoprevir) inhibited other SARS-COV-2 proteases, called Plotrotease. These results proved to be very important.
Remdesivir is the only approved antiviral drug for Covid-19, a protein targeting the SARS-COV-2 coronavirus, called RNA polymerase, which synthesizes viral RNA. Since the production of functional RNA polymerase requires two SARS-COV-2 proteases, HCV drugs may improve the efficacy of Remdesivir in inhibiting viral replication. Researchers show that only four HCV drugs targeting the unexpected SARS-COV-2 PLOTESE improve the efficacy of Remdesivir by up to 10 times. In contrast, HCV drugs targeting the main protease of SARS-COV-2 did not improve the efficacy of Remdesivir.
As described in this article, “HCV drugs that strongly synergize with Remdesivir are most relevant to the goals of this study. The reused drug itself may not have sufficient inhibitory activity to achieve clinical efficacy. Synergistic effects with Remdesivir increase the proposed reused HCV The efficacy of drugs and Remdesivir.”
“Identification of PLPRO as an antiviral target that has synergistic effects with Remdesivir is a very important finding. We hope that this work will encourage the fusing of specific SARS-COV-2 PLPRO inhibitors with polymerase inhibitor combination therapy to Produce highly efficient antiviral cocktails, which will also prevent the rise of drug resistance mutations,” Kris White said.
As Adolfo Garcia-Sastre stressed: “Combining the use of Remdesivir
Covid-19-treated PL proteases will also reduce the likelihood of selecting SARS-COV2 virus. ”
HCV medications are taken orally, while Remdesivir is given intravenously. Therefore, treatment for COVID-19 patients with a combination of Remsville and HCV drugs must be performed in the hospital. The results of this article strongly support the establishment of clinical trials to test drug combinations in hospitalized patients.
Furthermore, as Krug said: “Our goal is to develop a combination of oral drugs that can be used before outpatients get sick to need hospitalization so that they can use it. To this end, it is necessary to determine SARS inhibition. – Oral medications for COV-2 polymerase to develop effective outpatient treatments.”
Journal Reference and Major Image Credit:
Bafna, K., White, K., Harish, B., Rosales, R., Ramelot, TA, Acton, TB, Moreno, E., Kehrer, T., Miorin, L., Royer, Royer, CA, García -Sastre, A., Krug, RM, & Montelione, GT (2021). Hepatitis C virus drug that inhibits SARS-COV-2 papaya-like proteases and Remdesivir in synergistically inhibit viral replication in cell culture. Cell Reports, 35(7), 109133.
