Sofosbuvir with Ledipasvir and Daclatasvir: Scientists recommend better alternative to Remdesivir

NEW DELHI: At a time when the country is facing a shortage of Remdesivir, scientists have investigated 61 antiviral drugs and found a combination that has superior anti-SARS-CoV-2 potential.

A team of scientists from the Biochemical Sciences Division, CSIR-National Chemical Laboratory, India Academy of Scientific and Innovative Research (AcSIR), Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, and INTOX Private Limited, Pune worked on the efficacy of drug repurposing for treating Covid-19.

“Our analysis suggested Sofosbuvir in combination with Ledipasvir and Daclatasvir as potential therapeutic agents for SARS-CoV-2. The combined score suggests that these combinations have superior anti-SARS-CoV-2 potential than Remdesivir and other investigational drugs,” they said in a paper published in Current Science.

They said the present work provides a rationale-based approach to select drugs with possible anti-SARS-CoV-2 activity for further clinical evaluation. With the shortage of Remdesivir, the combination can be used to save the lives of severe Covid-19 patients. 

“Drug repurposing has been utilized as the most preferred therapeutic intervention for COVID-19 mitigation due to its necessity and feasibility. To prioritize therapeutic regime against COVID-19, we used 61 antiviral drugs and their combinations,” said the paper.

Selected molecules were subjected to virtual screening against -- human angiotensin-converting enzyme 2 receptor-binding domain (hACE-2) which serves as an anchor for virus attachment and entry, SARS-CoV-2 RNA dependent RNA polymerase (RdRp) responsible for viral RNA replication, and SARS-CoV-2 main protease (MPro) needed for viral polyprotein slab proteolytic processing.

“Based on docking score, pharmacodynamic and pharmacokinetic parameters, combinations of Daclatasvir, Elbasvir, Indinavir, Ledipasvir, Paritaprevir, and Rilpivirine were analysed further. Our analysis suggested Sofosbuvir in combination with Ledipasvir and Daclatasvir as potential therapeutic agents for SARS-CoV-2,” it added.

The team said that the findings provide a scientific rationale for applying Ledipasvir and Daclatasvir in combination with Sofosbuvir for COVID-19 management.

“Recent initial clinical trial data from Iran with Ledipasvir and Daclatasvir in combination with Sofosbuvir against COVID-19 are encouraging. Based on our analysis and available preclinical and clinical data, we recommend prioritization and aggressive perusal of clinical evaluation of these drug combinations,” it further said.