A new study has identified a variety of as yet unexplored ways to attack the mutating SARS-CoV-2 virus, including drugs and possible cocktails that are shown to target vital proteins of the novel coronavirus.

Researchers from KTH Royal Institute of Technology (Stockholm, Sweden), in collaboration with Alagappa University (Karaikudi, India) have proposed a list of individual drugs and cocktails that deserve testing for the treatment of COVID-19. The researchers at KTH tested their own screening protocol, as an alternative to software typically used in the biopharmaceutical industry to screen vast volumes of compounds in drug databases. Theirs involved a double-scoring approach to identify lead compounds that show potential for COVID-19 therapy. The procedure appears to have succeeded in avoiding false-positives - a common problem in virtual screening.

A key part of the study 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 the researchers, multi-targeting offers an effective route to deal with drug resistance, which would enable a drug to work around mutations of the virus. This attribute allowed the team to propose cocktails that have versatility. For example, the study proposed one cocktail, Baloxavir marboxil, Natamycin and RU85053, which targets the three viral proteins respectively, 3CL Main protease, papain-like protease and RdRp. Such drug cocktails have proven effective in the treatment of other virally-transmitted diseases, such as HIV.

The researchers believe that the reliability of their approach was validated by the fact that the screening also identified drugs that are already in clinical trial. Furthermore, such studies can provide valuable insights regarding why certain drugs were found to be ineffective. For example, the researchers have stated that the drug hydroxychloroquine was non-effective mainly due to its poor binding affinity towards viral proteins. Other drugs that the study recommended for testing were Tivantinib, Olaparib, Zoliflodacin, Golvatinib, Sonidegib, Regorafenib and PCO-371. The researchers also provided a listing of multi-targeting drugs such as DB04016, Phthalocyanine, Tadalafil, which can also be effective in combating the rapidly-mutating coronavirus.

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

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