2020/07/31 by Draško Tomić, Karolj Skala, Tomić, Draško +23
Medicine · Computer Science · #SARS-CoV-2 and COVID-19 Research #COVID-19 Clinical Research Studies #Computational Drug Discovery Methods
paper · pdf · doi:10.48550/arxiv.2007.16177
In this study, we investigated the inhibition of SARS-CoV-2 spike\nglycoprotein with HIV drugs and their combinations. This glycoprotein is\nessential for the reproduction of the SARS-COV-2 virus, so its inhibition opens\nnew avenues for the treatment of patients with COVID-19 disease. In doing so,\nwe used the VINI in silico model of cancer, whose high accuracy in finding\neffective drugs and their combinations was confirmed in vitro by comparison\nwith existing results from NCI-60 bases, and in vivo by comparison with\nexisting clinical trial results. In the first step, the VINI model calculated\nthe inhibition efficiency of SARS-CoV-2 spike glycoprotein with 44 FDA-approved\nantiviral drugs. Of these drugs, HIV drugs have been shown to be effective,\nwhile others mainly have shown weak or no efficiency. Subsequently, the VINI\nmodel calculated the inhibition efficiency of all possible double and triple\nHIV drug combinations, and among them identified ten with the highest\ninhibition efficiency. These ten combinations were analyzed by Medscape\ndrug-drug interaction software and LexiComp Drug Interactions. All combinations\nexcept the combination of cobicistatabacavirrilpivirine appear to have\nserious interactions (risk rating category D) when dosage\nadjustments/reductions are required for possible toxicity. Finally, the VINI\nmodel compared the inhibition efficiency of cobicistatabacivirrilpivirine\ncombination with cocktails and individual drugs already used or planned to be\ntested against SARS-CoV-2. Combination cobicistatabacivirrilpivirine\ndemonstrated the highest inhibition of SARS-CoV-2 spike glycoprotein over\nothers. Thus, this combination seems to be a promising candidate for the\nfurther in vitro testing and clinical trials.\n