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chemistry and molecular biology

Researchers identified potential inhibitors of SARS-CoV-2 infection

Credit: PIRO4D
Credit: PIRO4D
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The number of people infected with SARS-CoV-2 continues to rise as of May 2020. Every year, emerging and re-emerging viruses surface from natural reservoirs to infect humans. We have seen a large spread of viruses like MERS, Zika and Ebola in the past years. Therefore, it is clear that in order to manage pandemics, we need more effective and faster solutions.

Developing virus-specific vaccines and drugs is time consuming and costly. On the other hand, safe-in-man broad-spectrum antivirals are a ready to use option that could have an important role in the battle against SARS-CoV-2 and other viral diseases. This saves time and resources required for the development of new virus-specific vaccines and drugs. They could also have a global impact by decreasing both morbidity, mortality and improve the outlook of infected patients.

Broad-spectrum antivirals

Broad-spectrum antivirals are small molecules that inhibit viruses belonging to two or more viral families. The molecules are used in treatment for viral infections and many of them show efficacy against other viruses outside their original indication. The strategy is called drug repurposing, also known as repositioning. The cost and timeline for clinical availability is significantly reduced compared to new vaccines and medicines. Previous analysis has shown that the cost of using antiviral treatment costs could be reduced up to 50%.

Antivirals for SARS-CoV-2

The University of Tartu and the Norwegian University of Science and Technology researchers have recently reviewed and summarized the information of safe-in-man antiviral molecules, and gathered it in a freely accessible database. As a result of screening 136 safe-in-human broad-spectrum antivirals, six agents for SARS-CoV-2 inhibition were found: nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. One of the discovered agents, Nelfinavir (also known as Viracept) is today used as a treatment for HIV. It also inhibits other viruses such as HCV and SARS. Combinations of virus-directed nelfinavir with host directed drugs were even more efficient. (The results have been uploaded into online archive BioRxiv for public dissemination and critical review. To be published in a scientific journal, the article must pass the corresponding peer-review and editing process.)

“We are applying the principle of drug repurposing, meaning that we aim to treat coronavirus infection by using compounds originally intended for another disease. By this, we can generate additional value for drugs already on the market. This gives them significant advantages over the development of new vaccines and drugs,” explained Denis Kainov, Senior Research Fellow in Virology at the University of Tartu and Associate Professor of Norwegian University of Science and Technology (NTNU). “The development of new drugs is very expensive and time-consuming, but this process has already been completed for the compounds we have identified. An additional significant advantage of antiviral compounds is the fact that we can use them both for the treatment and prevention of viral diseases,” Kainov added.

According to the researchers, these coronavirus inhibitors can benefit the whole world, as they provide a quicker response both to the current pandemic and future viral outbreaks. They also help to manage pandemics better, considering the threat of emerging drug‑resistant strains by offering faster response in the form of repurposing drugs. This is due to the fact that a large database of antiviral agents allows scientists to screen large amounts of existing molecules that could potentially inhibit different viruses and its new strains.

Future goals with antiviral agents

The future goal of the research is to complete the preclinical studies and translate the findings into trials in patients. The antivirals or their combinations will have a global impact. They could be used for improving the protection of the general population from emerging and re-emerging viral infections. The researchers are also assembling a toolbox of antiviral compounds for the rapid and safe response to future viral outbreaks.

The information about the status of currently available and emerging anti-SARS-CoV-2 options is summarized in the freely accessible website that allows interactive exploration of the data. The database is updated as soon as novel anti-SARS-CoV-2 drugs emerge, or the statuses of existing ones are updated: https://sars-coronavirus-2.info

Additional information can be found here

Mare Vahtre, University of Tartu, Institute of Technology

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