Indian researchers find new potential COVID-19 drug treatments

Indian scientists have identified drugs and possible cocktails that can target vital proteins of the novel coronavirus, and may potentially help treat COVID-19.

Using a virtual screening of the DrugBank database, the research published in the journal Scientific Reports, identified a variety of unexplored ways to attack SARS-CoV-2, even as it mutates.

The Drugbank database is a chemical space of compounds approved by FDA and molecules under drug trials.

The researchers from Alagappa University in Tamil Nadu and KTH Royal Institute of Technology, Sweden propose a list of individual drugs and cocktails that deserve testing for the treatment of COVID-19.

A key part of the study, the researchers said, is the identification of drugs that target or bind to multiple proteins that are essential for replication of the virus, and which are also involved in the initial stage of host-cell infection.

According to Vaibhav Srivastava and Arul Murugan, the corresponding authors of the study, multi-targeting offers an effective route to deal with drug resistance, which would enable a drug to work around mutations of the virus.

“The virus is mutating rapidly, which means that it is modifying its proteins. If we have a drug that can target several proteins, and if one becomes mutated, the drug will be effective on others,” Srivastava said.

This attribute allowed the team to propose cocktails that have versatility.

“It was possible for us to propose cocktails, or blends of drugs, in which each drug can bind to a specific target protein with high affinity,” he said.

The study proposed one cocktail, baloxavir marboxil, natamycin and RU85053, which targets three viral proteins respectively, 3CL Main protease, papain-like protease and RdRp.

The researchers noted that such drug cocktails have proven effective in the treatment of other virally-transmitted diseases, such as HIV.

Murugan says that the reliability of their approach was validated by the fact that the screening also identified drugs that are already in clinical trial.

Such studies can provide valuable insights regarding why certain drugs were found to be ineffective, the researchers said.

For example, the drug hydroxychloroquine was non-effective mainly due to its poor binding affinity towards viral proteins, they said.

Other drugs that the study recommended for testing were tivantinib, olaparib, zoliflodacin, golvatinib, sonidegib, regorafenib and PCO-371.

The research also provides a listing of multi-targeting drugs such as DB04016, phthalocyanine, tadalafil, which can also be effective in combating the rapidly-mutating coronavirus.