Leaning on repurposed drug candidates to fight COVID-19

While vaccines have significantly reduced disease severity of and mortality from COVID-19, there is a need for responses to emerging variants of the virus.

“A promising strategy is to repurpose drugs already approved for other diseases,” said Seshadri Vasan, a virologist and project leader for COVID-19 at Australia's national science agency, CSIRO. Vasan led an international team to identify potential remedies for COVID-19 from existing drugs.

Researchers from India’s Birla Institute of Technology and Science (BITS) in Pilani played a key role in this study¹. CSIRO delegated the drug selection work to Monash University in Australia and BITS in India.

“Besides speeding up drug development, repurposing can reduce manufacturing costs,” says Sankaranarayanan Murugesan, associate professor of pharmacy and the lead investigator at BITS, which has a research group for computer-aided drug design. “For countries such as India, it’s not enough if a new or repurposed drug is effective against COVID-19. It must be affordable,” he said.

Currently, remdesivir is the only repurposed drug molecule approved by the US Food and Drug Administration (FDA). Four monoclonal antibodies directed toward the spike protein of COVID-19 have received FDA’s emergency-use authorisation, but doubts persist about their efficacy against “future variants with different spike protein structures”, he says.

Vasan and his co-workers started their search by assembling and curating a database consisting of 7,817 compounds selected from the Compounds Australia Open Drug Collection, a facility at Griffith University in Queensland, Australia. They narrowed the list to 214 potential drug molecules using eight filters to assess the attributes required for the drug to be safe and effective. These 214 molecules were further sorted based on their computed antiviral activity.

“The filtering process identified 12 FDA-approved molecules with established safety profiles that have plausible mechanisms for treating COVID-19 disease,” Vasan said. “In the next step, the 12 selected drugs will be evaluated against SARS-CoV-2 and its variants in relevant in-vitro/ ex-vivo models,” he says.

Vasan said the methodology developed by his team provides a template for prioritizing drug candidates to tackle COVID-19 that are safe, efficacious, and cost-effective. The authors have created an online database, CoviRx, to enable the global research community to access the data of over 7,000 potential drugs.

“Our free-to-access and user-friendly database (https://www.covirx.org/) can be updated as and when more assay data is available”, Vasan says, adding that the CoviRx.org database and website is owned and operated by BITS. “It was a huge effort involving engineering and pharmacy graduates”, Murugesan says. “We worked collaboratively with the Monash Institute of Pharmaceutical Sciences, Australia, as well as BITS Computer Science and Information Systems colleagues to create the covirx.org repurposing database”.

The researchers “have developed and reported a rigorous methodology to identify potential drug candidates for repurposing”, Colleen Fisher, head of the school of Population and Global Health at the University of Western Australia, told Nature India.