Researchers from India's Alagappa University in Tamil Nadu and KTH Royal Institute of Technology in Sweden have identified drugs and possible cocktails that can target novel Coronavirus proteins to treat the SARS-CoV-2 caused disease COVID-19.
As per the study published in the journal Scientific Reports, virtual screening of the DrugBank database, a chemical space of compounds approved by FDA and molecules under drug trials, has helped identify new ways to attack the novel Coronavirus, even as it mutates. The team of scientists from India and Sweden proposed a list of individual drugs and cocktails that need to be tested for COVID-19 treatment.
The Key Target
The scientists said that the key part of this research is the identification of some drugs which can target or bind proteins necessary for replication of the virus and involved in the initial stage of host-cell infection.
Two authors of the study, Vaibhav Srivastava and Arul Murugan, said that the multi-targeting procedure offers an effective route to deal with drug resistance, which would enable a medication to work around mutations of the virus.
According to Srivastava, the virus is mutating rapidly and it means that the pathogen is modifying its proteins. In this case, he suggested that "if we have a drug that can target several proteins, and if one becomes mutated, the drug will be effective on others".
To achieve what Srivastava suggested, the team proposes 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," said the author.
The study proposed one cocktail, baloxavir marboxil (antiviral medication for influenza), natamycin (antifungal medication), and RU85053 (compound belongs to the class of organic compounds known as dipeptides), which targets the three viral proteins respectively, 3CL Main protease, papain-like protease, and RdRp. Such cocktails have proven effective in the treatment of HIV and other virally-transmitted diseases.
Another author of the study, Murugan said that the reliability of their approach was validated by the fact that their screening also identified drugs that are in the clinical trials. According to him, such studies can provide required insights into why some drugs were found to be ineffective against the COVID-19 treatment. For example, the highly popular hydroxychloroquine (HCQ), which was earlier promoted by US President Donald Trump, as well as many experts. HCQ was found to be non-effective mainly because of its poor binding affinity towards the viral proteins.
There are other drugs that the study recommended for testing and the list includes names like tivantinib, olaparib, zoliflodacin, golvatinib, sonidegib, regorafenib, and PCO-371. The study also added some multi-targeting drugs, DB04016, phthalocyanine, and tadalafil that can also be effective in fighting against the rapidly-mutating novel Coronavirus.