Scientists, including those of Indian-origin, have identified 21 existing drugs that stop the replication of the novel coronavirus which causes COVID-19 in lab studies, an advance that may lead to the development of new therapeutic combinations against the disease.
The researchers, including those from the Sanford Burnham Prebys Medical Discovery Institute in the US, analysed one of the world''s largest collections of known drugs for their ability to block the replication of the novel coronavirus, and found 100 molecules with confirmed antiviral activity in laboratory tests.
According to the study, published in the journal Nature, 21 of these drugs are effective in blocking the reproduction of the virus at concentrations that could be safely achieved in patients.
It said four of these compounds could work in combination with remdesivir, a current standard-of-care treatment for COVID-19.
"Remdesivir has proven successful at shortening the recovery time for patients in the hospital, but the drug doesn''t work for everyone who receives it. That''s not good enough," said Sumit Chanda, director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study.
"The urgency remains to find affordable, effective, and readily available drugs that can complement the use of remdesivir, as well as drugs that could be given prophylactically or at the first sign of infection on an outpatient basis," Chanda said.
In the study, the scientists performed extensive testing and validation studies, including evaluating the drugs on human lung biopsies that were infected with the virus, evaluating the drugs for synergies with remdesivir, and establishing dose-response relationships between the drugs and antiviral activity.
Of the 21 drugs that were effective at blocking viral replication, the scientists found that 13 have previously entered clinical trials for other indications and are effective at concentrations, or doses, that could potentially be safely achieved in COVID-19 patients.
They said two are already approved by the US Food and Drug Administration (FDA) -- astemizole (allergies), clofazamine (leprosy) -- and remdesivir has received Emergency Use Authorization from the agency.
According to the study, four of the drugs worked synergistically with remdesivir, including the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug that has reached Phase 3 clinical trials.
"This study significantly expands the possible therapeutic options for COVID-19 patients, especially since many of the molecules already have clinical safety data in humans," Chanda said.
"This report provides the scientific community with a larger arsenal of potential weapons that may help bring the ongoing global pandemic to heel," he added.
The researchers are currently testing all 21 compounds in small animal models and "mini lungs," or lung organoids, that mimic human tissue.
If these studies are favorable, the team will approach the U.S. Food and Drug Administration (FDA) to discuss a clinical trial(s) evaluating the drugs as treatments for COVID-19.
"Based on our current analysis, clofazimine, hanfangchin A, apilimod and ONO 5334 represent the best near-term options for an effective COVID-19 treatment," Chanda said.
"While some of these drugs are currently in clinical trials for COVID-19, we believe it''s important to pursue additional drug candidates so we have multiple therapeutic options if SARS-CoV-2 becomes drug resistant," he added.
According to the scientists, the drugs were first identified by a rapid screening of more than 12,000 drugs from the ReFRAME drug repurposing collection, which they said is a comprehensive drug repurposing collection of compounds approved by the FDA for other diseases, or tested extensively for human safety.
"We realised early in the COVID-19 pandemic that ReFRAME would be an invaluable resource for screening for drugs to repurpose against the novel coronavirus," said Arnab Chatterjee, a co-author on the paper.