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Sofosbuvir combined with other antivirals can fight Covid-19

SARS-CoV-2 exonuclease-based proof reader maintains the accuracy of viral RNA genome replication to sustain virulence

Wednesday October 7, 2020 7:05 PM, IANS


New York: Researchers have demonstrated that RNA terminated by hepatitis-C drug Sofosbuvir may be more effective against the Covid-19 virus.

The results, published in the journal Scientific Reports, support the use of the USFDA-approved hepatitis-C drug EPCLUSA -- Sofosbuvir/Velpatasvir -- in combination with other antiviral drugs in Covid-19 clinical trials.

The SARS-CoV-2 exonuclease-based proof reader maintains the accuracy of viral RNA genome replication to sustain virulence.

Any effective antiviral targeting the SARS-CoV-2 polymerase must therefore display a certain level of resistance to this proof reading activity, according to the researchers.

"We found that the RNA terminated by Sofosbuvir resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a Covid-19 therapeutic," said the study authors from Columbia University in the US.

The new study builds upon earlier work the researchers have conducted.

Last January, before Covid-19 reached pandemic level, the team posited that EPCLUSA might inhibit SARS-CoV-2, the virus responsible for Covid-19.

Their reasoning was based on the analysis of the molecular structures and activities of hepatitis-C viral inhibitors and a comparison of hepatitis-C virus and coronavirus replication.

In a study, the researchers showed that the active drug Sofosbuvir triphosphate is incorporated by SARS-CoV and SARS-CoV-2 polymerases, shutting down the polymerase reaction.

A polymerase is an enzyme that synthesizes long chains of polymers or nucleic acids.

Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells.

Currently, Covid-19 clinical trials with a number of hepatitis-C drugs such as EPCLUSA and the combination of Sofosbuvir and Daclatasvir (which is similar to Velpatasvir) are ongoing in several countries.

The research team noted that a recent preprint from the University of California Berkeley indicates that a combination of Remdesivir and EPCLUSA increases Remdesivir's efficacy 25-fold in inhibiting the Covid-19 virus.

"These results offer a molecular basis supporting the study of EPCLUSA in combination with Remdesivir for Covid-19 clinical trials," the team concluded.


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