Image: KTH researchers tested their own detection protocol that appears to have reduced false positive matches (Photo courtesy of KTH)
A new study has identified a variety of as yet unexplored ways to target the mutant SARS-CoV-2 virus, including drugs and possible cocktails that have been shown to target vital proteins from the new coronavirus.
Researchers from the 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 to be evaluated for the treatment of COVID-19. The KTH researchers tested their own detection protocol, as an alternative to the software commonly used in the biopharmaceutical industry to analyze large volumes of compounds in drug databases. His involved a double-scoring approach to identify leading compounds that show potential for COVID-19 therapy. The procedure appears to have managed to avoid false positives, a common problem in virtual detection.
A key part of the study is the identification of drugs that target (or bind) multiple proteins that are essential for virus replication and that are also involved in the early stage of host cell infection. According to the researchers, multisectoring offers an effective route to cope with drug resistance, which would allow a drug to avoid virus mutations. This attribute allowed the team to propose cocktails that have versatility. For example, the study proposed a cocktail, Baloxavir marboxil, natamycin, and RU85053, which targets the three viral proteins respectively, 3CL major protease, papain-like protease, and RdRp. These drug cocktails have been shown to be effective in treating 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 trials. Additionally, these studies can provide valuable information on why certain medications were found to be ineffective. For example, researchers have stated that the drug hydroxychloroquine was ineffective primarily due to its low binding affinity for viral proteins. Other drugs the study recommended for testing were Tivantinib, Olaparib, Zoliflodacin, Golvatinib, Sonidegib, Regorafenib, and PCO-371. The researchers also provided a list of multi-sector drugs such as DB04016, Phthalocyanine, Tadalafil, which may also be effective in fighting the rapidly mutating coronavirus.
“The virus is mutating rapidly, which means it is modifying its proteins,” said researcher Vaibhav Srivastava. “If we have a drug that can target multiple proteins, and if one mutates, the drug will be effective on others.”
KTH Royal Institute of Technology