We built the CoviRx database through BITS Pilani to help identify drugs that could be repurposed for COVID-19
Professor Seshadri Vasan, Honorary Professor of Medical and Health Sciences at Edith Cowan University (Australia) and University of York (England) and BITS Pilani alumnus, discusses a study on why some osteoporosis drugs may protect against COVID-19, highlighting findings from the CoviRx database and their potential implications for future treatments, in an interview with Express Pharma
1) How was the ‘CoviRx’ drug repurposing database used to identify promising bisphosphonates?
We built the CoviRx database through BITS Pilani to help identify drugs that could be repurposed for COVID-19. We performed a methodical down-selection of nearly eight thousand approved drugs on CoviRx and noticed that alendronate was amongst the candidates that looked promising against COVID-19. As it is a bisphosphonate, we then decided to look at all bisphosphonates in another global database, and identified seven promising leads including zoledronate and minodronate. Our work happened in parallel to the Harvard study, which retrospectively looked at over 450 thousand bisphosphonate users matched to non-users. They found that those who used drugs such as alendronate and zoledronate had reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis and related hospitalisation, but did not provide a molecular explanation for this. Our work bridges this crucial gap.
2) How do bisphosphonates potentially offer protection against Covid-19?
There are prodrugs like remdesivir which inhibit RdRp, which is a key enzyme for coronavirus replication. The promising bisphosphonates we have identified through molecular modelling also appear to bind competitively in a similar fashion, and this could explain the protective effects observed by Harvard.
3) What further studies and human clinical trials are planned to explore the potential of osteoporosis drugs in treating Covid-19 and other coronaviruses?
All three drugs require further ‘prospective’ evaluation in different parts of the world because the Harvard study was retrospective and limited to US population. However, minodronate is only approved in Japan so studies have to be there.
4) Why is there a need for new drugs to combat the continuously mutating virus, despite the effectiveness of vaccines?
With some diseases like smallpox and polio, vaccines have an extremely high likelihood of preventing a person from getting the disease and stopping community transmission. With a continuously mutating virus like SARS-CoV-2, vaccines are still effective in reducing the odds of getting a severe disease and slowing down community transmission, but we need treatment options as well. We currently have drugs like paxlovid and remdesivir but it is important to have a wider range of treatment options that are not only safe and effective, but also affordable for developing countries.
5) How can existing drugs developed for other conditions be leveraged to combat Covid-19?
Sometimes through serendipity, and often by observing patients who take certain drugs versus those who don’t, we find evidence that certain drugs appear to offer a level of protection. These lead to methodical studies similar to the one by Harvard. Computational approaches like ours can complement this by rapidly screening thousands of compounds against important targets. In our case we investigated all bisphosphonates that bind competitively to a RdRp-associated domain called NiRAN to identify leads. This is important because it may be useful not only against COVID-19 but also future coronaviral outbreaks.